ovalbumin and Rhinitis--Allergic

Allergic rhinitis (AR) is a chronic, non-infectious inflammatory disease of the nasal mucosa, primarily mediated by specific immunoglobulin E (IgE), affecting approximately 10%-20% of the world's population. While immunofluorescence (IF) staining has long been a standard technique for detecting disease-specific protein expression, conventional IF techniques are limited in their ability to detect the expression levels of three or more proteins in the same sample. Consequently, multicolor IF techniques have been developed in recent years, which allow the simultaneous labeling of multiple targets in cells or tissues. This protocol provides a comprehensive overview of the process for establishing a rat model of AR, obtaining nasal mucosal samples, and the technical procedures for multicolor immunofluorescence. All rats in the AR group exhibited typical symptoms such as sneezing, a runny nose, and an itchy nose, with behavioral observations scoring ≥5 points. Hematoxylin and eosin (H&E) staining revealed increased inflammatory cell counts and disrupted nasal mucosal integrity in the AR group. Multicolor immunofluorescence (mIF) demonstrated increased expression of RORγt and TICAM-1, while Foxp3 expression decreased in the nasal mucosa tissue of AR rats.

Topics: Animals; Coloring Agents; Disease Models, Animal; Immunoglobulin E; Nasal Mucosa; Ovalbumin; Rats; Rhinitis, Allergic

We investigate whether lycopene has a protective effect in an experimental rat model of allergic rhinitis.. Experimental animals (65 rats) were randomized to 7 groups (Sham-Control, Lycopene 10 mg/kg/day, Lycopene 20 mg/kg/day, Intranasal lycopene drops, Intranasal steroid, Corn oil, Allergic Rhinitis). Rats were sensitized by administering of ovalbumin intraperitoneally and intranasally. In addition to ovalbumin; lycopene, corn oil and steroids were given to the relevant groups. Nasal symptom scores of the rats were recorded throughout the study. At end of the study, after intracardiac blood sample collection, all rats were sacrificed, and nasal tissues were examined histopathologically. Serum total immunoglobulin E (IgE) and ovalbumin (OVA) specific IgE were studied from all rats before and after the study.. There was a statistically significant increase (p < 0.05) in OVA specific IgE values measured before and after the study in all groups except the sham group. In serum total IgE values; there was a statistically significant increase after treatment in allergic rhinitis, corn oil, lycopene 10 mg and intranasal lycopene drops group, but other groups did not show any significant change. Histopathological study with hematoxylin-eosin staining and cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9), vasoactive intestinal peptide (VIP) expression found that lycopene suppresses inflammation with both nasal administration and increased dose. Nasal symptom scores were observed to decrease significantly in all lycopene and steroid groups compared to allergic rihinits and corn groups.. It was determined that lycopene were effective in the treatment of allergic rhinitis, and this effect was found to be stronger with increasing doses of lycopene.

Topics: Animals; Disease Models, Animal; Immunoglobulin E; Lycopene; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rats; Rhinitis, Allergic

Biyuan Tongqiao granule (BYTQ) is a traditional Chinese medicine that has been used in China to clinically treat patients with allergic rhinitis (AR), yet its underlying mechanism and targets remains unclear.. The study aimed to investigate the potential mechanism of BYTQ against AR using the ovalbumin (OVA) -induced AR mice model. Integrating network pharmacology and proteomics to investigate possible targets of BYTQ for AR.. The compounds in BYTQ were analyzed using UHPLC-ESI-QE-Orbitrap-MS. The OVA/Al(OH). A total of 58 compounds were identified from BYTQ. BYTQ significantly suppressed AR symptoms by inhibiting the release of OVA-specific immunoglobulin E (IgE) and histamine, improving the pathological injury of nasal mucosal tissue, and regulating the proportions of lymphocytes to maintain immune balance. Proteomics analysis showed that the cell adhesion factors and focal adhesion pathway might be potential mechanism of BYTQ against AR. The levels of E-selectin, vascular endothelial cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) proteins in the nasal mucosal tissue were significantly downregulated in the BYTQ-H group compared to the AR group. Integrating network pharmacology and proteomics analysis identified that SRC, PIK3R1, HSP90AA1, GRB2, AKT1, MAPK3, MAPK1, TP53, PIK3CA, and STAT3 may be potential protein targets for BYTQ to treat AR. Molecular docking analysis indicated that the active compounds of BYTQ could bind tightly to these key targets. In addition, BYTQ could inhibit OVA-induced phosphorylation levels of PI3K, AKT1, STAT3 and ERK1/2. The CETSA data suggested that BYTQ could improve the heat stability of PI3K, AKT1, STAT3 and ERK1/2.. BYTQ suppresses E-selectin and VCAM-1 and ICAM1 expression by regulating PI3K/AKT and STAT3/MAPK signaling pathways, thus alleviating inflammation in AR mice. BYTQ is the aggressive treatment for AR.

Topics: Animals; Cytokines; E-Selectin; Medicine, Chinese Traditional; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Network Pharmacology; Ovalbumin; Phosphatidylinositol 3-Kinases; Proteomics; Rhinitis, Allergic; Vascular Cell Adhesion Molecule-1

To investigate the therapeutic effect of Bicalutamide, an androgen receptor antagonist on the onset and development of allergic rhinitis in an animal model.. 40 male BALB/c mice were randomly divided into five groups (eight mice per group). Aluminum hydroxide powder was used as an adjuvant, combined with Ovalbumin (OVA) to establish the mouse model of allergic rhinitis via ultrasonic nebulization of OVA to stimulate the nasal cavity. Mice in Bica#1 group were intraperitoneally injected with 0.02 mg Bicalutamide/0.5 ml of normal saline daily for 7 consecutive days; mice in Bica#2 group were administered 0.02 mg Bicalutamide/0.5 ml of normal saline via intraperitoneal injection for 5 consecutive days, and then the same amount of normal saline was injected intraperitoneally for 2 consecutive days. Enzyme-linked immunosorbent assay was adopted to detect the serological levels of IgE, IL-4, and IL-6 production. Eosinophil infiltration was observed under microscope after hematoxylin and eosin staining of nasal mucosa. Quantitative PCR and Western blot were employed for determination of histamine receptors mRNA expression and PI3K/PKB associated protein levels, respectively.. Histological analysis shown that allergic lesion was induced after OVA sensitization. Intraperitoneal injection with 0.02 mg Bicalutamide daily for 7 consecutive days significantly reduced the allergic lesion; however, mice injected with the same amount of normal saline at the same time demonstrated no allergic rhinitis symptoms. In addition, there was a significant reduction in eosinophils number in Bicalutamide treated mice (n = 8) compared to the OVA group (n = 8) (OVA: 19.6 ± 5.3 vs. Bica#1: 7.7 ± 0.8 vs. Bica#2: 9.4 ± 1.2, both p < 0.01). Furthermore, ELISA results revealed that the serological levels of IgE (OVA: 17.3 ± 1.7 µg/ml vs. Bica#1: 9.2 ± 0.6 vs. Bica#2: 10.4 ± 2.3, both p < 0.05), IL-4 (OVA: 164.3 ± 5.1 pg/ml vs. Bica#1: 110.2 ± 3.1 vs. Bica#2: 115.3 ± 4.1, both p < 0.05) and IL-6 (OVA: 167.3 ± 3.7 pg/ml vs. Bica#1: 117.5 ± 6.5 vs. Bica#2: 114.8 ± 2.4, both p < 0.05) were significantly decreased after two different dosage of Bicalutamide treatment. Similarly, histamine receptors in mast cells were significantly reduced after two different dosage of Bicalutamide treatment. More importantly, p-PKB protein was notably reduced after two different dosage of Bicalutamide treatment compared to the OVA group, mTOR protein levels were also down regulated after two different dosage of Bicalutamide treatment.. Our data demonstrated that androgen receptor antagonist Bicalutamide can significantly alleviate allergic rhinitis lesion in the animal model. PI3K/PKB activity in mast cells was suppressed after Bicalutamide injection. Our results provide important implication in allergic rhinitis prevention and treatment.

Topics: Androgen Receptor Antagonists; Animals; Cytokines; Disease Models, Animal; Immunoglobulin E; Interleukin-4; Interleukin-6; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Phosphatidylinositol 3-Kinases; Rhinitis, Allergic

Allergic rhinitis (AR) is an inflammatory disorder of nasal mucosa resulting from allergen exposure. Daphnetin (DAP) is a coumarin derivative that has various bioactivities. Nevertheless, its specific function in AR is unclear.. This study is aimed to explore the specific function of DAP in AR.. An AR murine model was established by ovalbumin (OVA) induction. Murine sneezing and rubbing behaviors were observed. Hematoxylin-eosin was used for histopathological observation of nasal mucosa. ELISA was utilized for detection of cytokine production in murine serum. Oxidative stress-associated markers were assessed by commercial assay kits. Western blotting was utilized for evaluating protein levels of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) in nasal mucosa.. DAP alleviated OVA-induced nasal symptoms, inflammatory response and oxidative stress in the AR murine model. DAP activated nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling and inactivated TLR4/NF-κB signaling in murine nasal mucosa.. DAP mitigates OVA-induced AR in mice by activating Nrf2/HO-1 signaling and inactivating TLR4/NF-κB signaling.

Topics: Animals; Disease Models, Animal; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-E2-Related Factor 2; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Toll-Like Receptor 4

Allergic rhinitis as common airway disease has high prevalence in all peoples worldwide. In allergic diseases, Th2 cells release type 2 cytokines that support the inflammation in airways. All the drugs used for allergic rhinitis do not cure completely, and the choice of drugs according to cost and efficacy is very important in all groups of atopic patients. Therefore, in this study, the effect of commercial drugs on cytokine gene expression has been studied. Male Balb/c mice were divided into six groups. Allergic rhinitis was induced in five of the six groups with ovalbumin, and four of these five groups were treated with salbutamol, budesonide, theophylline, and montelukast. The fifth group was used as positive control group and the sixth group as negative control group. For the survey, RNA was extracted, cDNA was synthesized, and quantitative real-time PCR was done for 21 genes. The four drugs had different effects on mRNA expression of cytokines (IL-1b, 2, 4, 5, 7, 8, 9, 11, 12, 13, 17, 18, 22, 25, 31, 33, 37, IFN-γ, TNF-α, TGF-β1, and eotaxin) in the allergic rhinitis groups. Salbutamol can be used during pregnancy and breastfeeding, but it has some side effects. Budesonide in the inhaled form is generally safe in pregnancy. Theophylline cannot control allergic attack in the long run. Montelukast is not useful in the treatment of acute allergic attacks. Immunomodulatory and anti-inflammatory effects of drugs in control of allergic rhinitis via Th2 cytokines can be new approaches in molecular medicine.

Topics: Albuterol; Animals; Budesonide; Cytokines; Disease Models, Animal; Gene Expression; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Theophylline

Allergic rhinitis (AR) is one of the most common inflammatory diseases. IgE, inflammatory cytokine production and Th17/Tregs imbalance have been implicated in AR pathogenesis. Bufotalin, a component extracted from toad venom skin secretions and auricular glands, has anti-inflammatory activity and regulates Th17/Tregs balance. Here, the effects of bufotalin on AR were explored.. The AR mice model was established using ovalbumin (OVA). AR mice were treated with bufotalin started on Day 22 with various doses (1, 10, 100 μg or 1 mg per mouse) every day to Day 30. The sneezing and rubbing frequencies were counted. Serum levels of IL-1β, IL-10 and OVA-specific IgE were measured. The superficial cervical lymph nodes were harvested and the percentage of Tregs in lymph node was determined using CD4 and Foxp3 markers.. OVA treatment successfully induced AR model in mice with significantly increased sneezing and rubbing frequency, elevated levels of serum histamine, IL-1β, IL-10 and OVA-specific IgE. Bufotalin treatment significantly ameliorated AR symptoms, with reduced histamine, IgE and IL-1β levels, as well as sneezing and rubbing frequency. Moreover, bufotalin treatment decreased the serum levels of IL-1β, IL-10 and OVA-specific IgE in AR mice.. Bufotalin ameliorated allergic rhinitis symptoms in AR mice by restoring Tregs in lymph node.

Topics: Animals; Cytokines; Disease Models, Animal; Histamine; Immunoglobulin E; Interleukin-10; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sneezing

Allergic rhinitis is a chronic inflammatory disease of the nasal mucosa affecting the quality of life of patients. SRY-box transcription factor 11 (SOX11) was reported to play important roles in inflammatory responses, but its role in AR is poorly understood.. To explore the role of SOX11 in the development of allergic rhinitis.. Cell culture and animal study.. An in vivo murine allergic rhinitis model was established using ovalbumin treatment in female mice. Interleukin-13-stimulated human nasal mucosa epithelial cells were used for in vitro studies. Expression levels of SOX11, epithelial-derived cytokines, and mucin were determined in both modesls.. SOX11 was highly expressed in allergic rhinitis mice. Allergy symptoms, serum ovalbumin-specific IgE, histamine, eosinophils, goblet cells, and type 2 cytokine secretion were increased in ovalbumin-treated mice. Furthermore, allergic rhinitis mice exhibited overproduction of epithelial-derived cytokines (thymic stromal lymphopoietin, interleukin-25, interleukin-33), C-C motif chemokine ligand 26 (CCL26), and mucin 5 AC (MUC5AC). Silencing SOX11 alleviated the behavioral symptoms and upregulation of epithelial-derived cytokines, CCL26, and MUC5AC. In human nasal mucosa epithelial cells, interleukin-13 enhanced SOX11 expression in a time-dependent manner, and signal transducer and activator of transcription 6 (STAT6) was involved in the interleukin-13-mediated expression of SOX11 by regulating transcription. Knockdown of SOX11 reduced epithelial-derived cytokine expression and MUC5AC levels in interleukin-13-treated human nasal mucosa epithelial cells.. SOX11 plays a critical role in allergic rhinitis development by regulating epithelial-derived cytokines and might be a new therapeutic target for allergic rhinitis.

Topics: Animals; Cytokines; Female; Humans; Interleukin-13; Mice; Mucins; Ovalbumin; Quality of Life; Rhinitis, Allergic; SOXC Transcription Factors

Inotodiol has been proven to have antitumor, antiviral, anti-inflammatory, and antiallergic properties. This study investigated the immunomodulatory capability of inotodiol in allergic rhinitis (AR) mice.. Forty BALB/c mice were divided into four groups, 10 mice each: control (CON), AR with phosphate-buffered saline (PBS) treatment (AR), inotodiol treatment (AR+Ino), and dexamethasone treatment (AR+Dex). Episodes of sneezing and nose rubbing were counted. Cytokines in nasal lavage fluid (NLF) and immunoglobulin in blood serum were measured. Nasal mucosae from each group were used for protein, reverse transcriptase-polymerase chain reaction (RT-PCR), and histological analyses. Splenocytes were cultured for evaluation of cytokine production in each group.. Symptoms of rubbing and sneezing improved in the group of AR+Ino and AR+Dex than in the AR. NLF in the AR+Ino and AR+Dex also showed a significant decrease in interleukin (IL)-5, IL-10, and IL-13 compared to the AR. In addition, the number of eosinophils, goblet cells, and mast cells were notably lower in the nasal mucosae of the AR+Ino and AR+Dex. IL-4 and IL-17A in the AR+Ino and AR+Dex groups were decreased compared to the AR. Chemokines related to mast cell degradation were also decreased in the AR+Ino and AR+Dex groups. Total immunoglobulin (Ig)E, specific IgE and ovalbumin (OVA)-specific IgG1, and histamine levels were also significantly lower in the AR+Ino and AR+Dex groups. IL-10 and IL-13 were notably increased in the splenocytes of the AR after OVA stimulation, whereas the other groups showed no change.. These results indicate inotodiol can help suppress allergic responses by immunomodulation activities.

Topics: Animals; Cytokines; Disease Models, Animal; Immunoglobulin E; Inflammation; Interleukin-10; Interleukin-13; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sneezing

As one of the most common allergic diseases, allergic rhinitis (AR) has attracted wide attention all over the world. More appropriate treatment of AR should be explored thoroughly. In recent years, traditional Chinese medicine has attracted more attention in AR treatment. As a classical Chinese medicine prescription, Xiaoqinglong decoction (XQLD) has been commonly used in treating AR. Even though its therapeutic effect on AR has been clinically confirmed, more molecular mechanism remains to be further investigated. Our research aimed to investigate the therapeutic mechanism of XQLD for AR management.. The study was evaluated in an ovalbumin sensitized mouse model and liquid chromatography-mass spectrometry was adopted to test the stability of XQLD's effective components.. The results confirmed the stability and safety of the effective components of XQLD. XQLD significantly downregulated the expression of HDACs (HDAC1, HDAC3, and HDAC4) and Th2 inflammatory factors (IL4, IL5, and IL13) in AR mice. XQLD and the HDAC inhibitor JNJ-26481585 promoted the expression of epithelial tight junction proteins (claudin-1 and ZO-1) and decreased the expression of mucins (Muc5ac and Muc5b) in the nasal mucosa of AR mice.. In conclusion, our findings present the beneficial effects of XQLD on AR and recovery of the nasal epithelium. We also identify the decreased HDAC as a potential target of XQLD for AR treatment. This study provides an important experimental proof for elucidating the therapeutic mechanism of XQLD.

Topics: Animals; Disease Models, Animal; Down-Regulation; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic

Prostaglandins (PGs) are bioactive lipid mediators derived from the nuclear and plasma membranes via the cyclooxygenase (COX) pathway of arachidonic acid (AA) metabolism. PGs bridge the interactions between various immunomodulatory cells in allergic rhinitis (AR) and are considered key players in regulating pro-inflammatory and anti-inflammatory responses. AA conversion to PGs involves rate-limiting enzymes that may be blocked by statins. The mechanisms by which statins regulate these enzymes in AR remain unclear. We investigated the effects of oral atorvastatin on PGs production in AR.. An ovalbumin-induced AR rat model was constructed and the changes in nasal symptom score and nasal mucosa histopathological characteristics of AR rats under different atorvastatin doses were assessed. qRT-PCR, western blotting, and immunofluorescence were used to detect the mRNA and protein expression levels of rate-limiting enzymes and downstream molecules of AA metabolism in the nasal mucosa and liver.

Topics: Animals; Anti-Inflammatory Agents; Atorvastatin; Cytokines; Disease Models, Animal; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-kappa B; Ovalbumin; Prostaglandins; Rats; Rhinitis, Allergic

DPP4 is thought to be involved in certain immune processes and plays an important role in allergic reactions in the lungs. The effect of the DPP4 inhibitor sitagliptin on the effector phase of allergic rhinitis (AR) in ovalbumin (OVA)-sensitized mice and on mast cell degranulation in vitro was assessed.. The AR mouse model was established by intraperitoneal injection combined with OVA intranasal method. OVA was injected intraperitoneally 3 times for the first 2 weeks, and the mice were subsequently given DPP4 inhibitors by oral gavage, accompanied by an OVA intranasal challenge. The impacts of DPP4 inhibitors on DPP4 levels in mouse model were determined. Nasal mucosa tissue was collected for H&E staining and toluidine blue staining. Immunoglobulin E (IgE) levels and histamine levels were analyzed, and IL-4, IL-5, and IL-12 as well as IFN-γ levels were assessed. Following the treatment of dinitrophenol (DNP)-IgE or DNP-IgE plus sitagliptin in RBL-2H3 cells, β-hexosaminidase activity was analyzed and toluidine blue staining was performed.. DPP4 level was reduced in AR patients, as well as in AR mouse models. Nasal allergic symptoms such as sneezing and nose-scratching showed high frequency in OVA-induced mice. Sitagliptin treatment during the intranasal challenge of OVA decreased DPP4 levels, suppressed allergic symptoms, eosinophil infiltration, IgE levels, mast cell infiltration, as well as the levels of inflammatory cytokines. We further found that sitagliptin inhibited mast cell activation and histamine levels in vitro.. Sitagliptin suppresses the effector phase of AR, and this mechanism is partly attributed to the suppression of inflammatory response and mast cell degranulation.

Topics: Animals; Cytokines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Histamine; Hypoglycemic Agents; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sitagliptin Phosphate; Tolonium Chloride

Allergic rhinitis (AR) is globally prevalent and its pathogenesis remains unclear. Alternative activation of macrophages is suggested in AR and thought to be involved in natural immunoregulatory processes in AR. Aberrant activation of Nod-like receptor protein 3 (NLRP3) inflammasome is linked with AR. Human placenta extract (HPE) is widely used in clinics due to its multiple therapeutic potential carried by diverse bioactive molecules in it. We aim to investigate the effect of HPE on AR and the possible underlying mechanism. Ovalbumin (OVA)-induced AR rat model was set up and treated by HPE or cetirizine. General manifestation of AR was evaluated along with the histological and biochemical analysis performed on rat nasal mucosa. A proteomic analysis was performed on AR rat mucosa. Mouse alveolar macrophages (MH-S cells) were cultured under OVA stimulation to investigate the regulation of macrophages polarization. The morphological changes and the expression of NLRP3 inflammasome and immunity-related GTPase M (IRGM) in nasal mucosa as well as in MH-S cells were evaluated respectively. The results of our study showed the general manifestation of AR along with the histological changes in nasal mucosa of AR rats were improved by HPE. HPE suppresses NLRP3 inflammasome and the decline of IRGM in AR rats and MH-S cells. HPE regulates macrophage polarization through IRGM/NLRP3. We demonstrated that HPE had protection for AR and the protection is achieved partly through suppressing M1 while promoting M2, the process which is mediated by IRGM via inhibiting NLRP3 inflammasome in AR.

Topics: Animals; Cytokines; Disease Models, Animal; Female; GTP-Binding Proteins; Humans; Inflammasomes; Macrophages; Mice; Nasal Mucosa; NLR Family, Pyrin Domain-Containing 3 Protein; NLR Proteins; Ovalbumin; Placenta; Placental Extracts; Pregnancy; Proteomics; Rats; Rhinitis, Allergic

Although recent studies have shown that the Notch signalling pathway induces the production of Th2-related immune factors, the exact mechanism through which Notch signalling exacerbates allergic rhinitis (AR) remains unknown. To investigate the roles of Notch in AR, serum, nasal mucosa and spleen samples were isolated from BALB/c mice. Paraffin sections were stained with haematoxylin and eosin (H&E) or periodic acid-Schiff (PAS) to assess inflammation. Flow cytometry was performed to detect group 2 innate lymphoid cells (ILC2s) in the serum samples, and cytokine levels were measured by enzyme-linked immunosorbent assays (ELISAs). The mRNA expression levels of the Notch signalling pathway components and miR-155 were measured by quantitative real-time PCR (qRT-PCR). In addition, human nasal epithelial cells (HNEpCs) were cultured to investigate the functional consequences of Notch pathway inhibition. The findings demonstrated that symptomatology and pathology were substantially altered, and AR model mice were established. In vivo stimulation with ovalbumin (OVA) significantly increased the Th2-type immune responses and the expression of OVA-sIgE, IL-4, GATA3, NF-κB and miR-155. However, the Notch signalling pathway was significantly deteriorated in AR, and this effect was accompanied by reduced Notch1, Notch2, RBPj and Hes1 levels. These effects were abrogated by gamma-secretase inhibitor IX (DAPT) treatment, and DAPT inhibited the wound healing and proliferation of HNEpCs in a dose-dependent manner. Therefore, our results suggest that blocking the Notch pathway may alleviate miR-155-mediated inflammation via the regulation of immune homeostasis in AR.

Topics: Animals; Cytokines; Disease Models, Animal; Humans; Immunity, Innate; Inflammation; Lymphocytes; Mice; Mice, Inbred BALB C; MicroRNAs; Nasal Mucosa; Ovalbumin; Receptors, Notch; Rhinitis, Allergic; Signal Transduction

Increasing studies have demonstrated that ginsenoside Rg3 (Rg3) plays an important role in the prevention and treatment of various diseases, including allergic lower airway inflammation such as asthma. To investigate the role of Rg3 in allergic upper airway disease, the effect and therapeutic mechanism of Rg3 in allergic rhinitis (AR) were studied. Ovalbumin-induced AR model mice were intragastrically administered with Rg3. Nasal symptoms, levels of IgE, IL-4, IL-5, IL-13, SOD and MDA in serum, and histopathological analysis of nasal mucosa were used to evaluate the effect of Rg3 on ameliorating AR in mice. Moreover, nasal mucosa samples from the normal control group, AR model group and high dosage of Rg3 were collected to perform omics analysis. The differentially expressed genes and significantly changed metabolites were screened based on transcriptomics and metabolomics analyses, respectively. Integrative analysis was further performed to confirm the hub genes, metabolites and pathways. After Rg3 intervention, the nasal symptoms and inflammatory infiltration were effectively improved, the levels of IgE, IL-4, IL-5, IL-13 and MDA were significantly reduced, and the level of SOD was obviously increased. The results of the qRT-PCR assay complemented the transcriptomic findings. Integrated analysis showed that Rg3 played an anti-AR role mainly by regulating the interaction network, which was constructed by 12 genes, 8 metabolites and 4 pathways. Our findings suggested that Rg3 had a therapeutic effect on ovalbumin-induced AR in mice by inhibiting inflammation development and reducing oxidative stress. The present study could provide a potential natural agent for the treatment of AR.

Topics: Animals; Cytokines; Disease Models, Animal; Immunoglobulin E; Inflammation; Interleukin-13; Interleukin-4; Interleukin-5; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Superoxide Dismutase; Transcriptome

BALB/c and C57BL/6 mouse strains are commonly used in allergy research. The current study investigated the immunological differences between these two mouse strains with a locally allergic rhinitis model.. Eighteen BALB/c and eighteen C57BL/6 mice received different doses of ovalbumin (OVA) intranasally for eight weeks (each mouse strain has three subgroups, 25 mg/mL group, 0.25 mg/mL group, and the PBS group). The allergic symptoms, OVA-specific serum antibody (IgE, IgG1, IgG2a), cytokines (IL-4, IFN-γ, IL-10) in the splenic culture supernatant, infiltrating eosinophils and goblet cells in local nasal mucosa were measured. RNA-seq technology was applied to detect differential gene expression in the local nasal mucosa.. With the same dose of OVA stimulation, the exacerbation of allergic symptoms was more pronounced in C57BL/6 than in BALB/c. BALB/c serum IgE, IgG1, and IgG2a gradually increased, and C57BL/6 produced fewer serum antibodies IgE and IgG1, while IgG2a never increased. BALB/c spleen cell culture supernatant IL-4 and IL-10 increased with increasing dose, and IFN-γ increased significantly in the intermediate dose group, while IL-4, IL-10, and IFN-γ did not increase in C57BL/6. The infiltration of eosinophils and goblet cells in both mice was proportional to the dose, while C57BL/6 was elevated more than BALB/c. RNA-seq suggested that the innate immune response, immune system process function, Jun kinase (JNK) pathway, and MAPKK pathway were upregulated in C57BL/6 compared to BALB/c. The core genes responsible for the differential immune response in both mice with allergic rhinitis were Kng2, Kng1, Gnb3, Lpar3, Lpar1, Pik3r1, Pf4, Apob, Rps9, and Fbxo2.. There are significant differences in the immunologic responses between BALB/c mice and C57BL/6 mice. BALB/c mice developed mild local allergic inflammatory reactions and strong systemic immune responses. In contrast, C57BL/6 mice had stronger local allergic inflammatory responses and relatively mild systemic immune responses. Different mice strains can be selected according to the research purpose.

Topics: Animals; Cytokines; Disease Models, Animal; Immunity; Immunoglobulin E; Immunoglobulin G; Interleukin-10; Interleukin-4; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic

Nasal eosinophilic inflammation is the therapeutic target for olfactory dysfunction in allergic rhinitis (AR). Intranasal corticosteroids are commonly considered to offer targetable benefit given their immunosuppressive property. However, experimental evidence suggests that continuous corticosteroid exposure may directly cause olfactory damage by disrupting the turnover of olfactory sensory neurons (OSNs). This potentially deleterious effect of corticosteroids calls into question their long-term topical use for treating olfactory loss related to AR. The aim of this study was to assess the impacts of chronic intranasal corticosteroid treatment on olfactory function and OSN population in mice under normal and pathological conditions.. BALB/c mice were intranasally treated with fluticasone propionate (FP, 0.3 mg/kg) for up to 8 weeks. Additional mice were used to establish an ovalbumin-induced mouse model of AR, followed by nasal challenge with ovalbumin for 8 weeks in the presence or absence of intranasal FP treatment. The authors examined olfactory function, OSN existence, neuronal turnover, and nasal inflammation using behavioral test, histological analyses, Western blotting, and enzyme-linked immunosorbent assay.. Intranasal treatment with FP for 8 weeks (FP-wk8) reduced odor sensitivity in normal mice. This reduction was concomitant with loss of OSNs and the axons projecting to the olfactory bulb, primarily resulting from increased neuronal apoptosis. In FP-wk8 AR mice, intranasal FP treatment attenuated olfactory impairment and eosinophilic inflammation but failed to reconstitute OSN population and axonal projections.. These results suggest that chronic intranasal corticosteroid treatment contributes to OSN degeneration that may reduce the therapeutic effectiveness for AR-related olfactory loss.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Animals; Inflammation; Mice; Olfactory Receptor Neurons; Ovalbumin; Rhinitis, Allergic

Substance P is a peptide from the tachykinin family, which is found in peripheral and central nervous systems, causing vasodilation and increased secretion in the nasal mucosa. In this study, we aimed to investigate whether the experimental model of allergic rhinitis will cause allergic changes in the larynx and to compare the effects of aprepitant, a substance P antagonist, on nasal symptoms in allergic rhinitis, and histopathological changes in the nasal and laryngeal mucosa with antihistamine and leukotriene receptor antagonists (LTRA).. An experimental animal study.. The study was carried out on 34 healthy 8-12 weeks old female Sprague Dawley rats in 5 groups. The rats in which an experimental allergic rhinitis model was created with ovalbumin were scored by observing their nasal symptoms, and nasal and laryngeal mucous membranes included in the study were evaluated histopathologically after medications.. As a result of the analysis of the data obtained from the study, antihistamine and LTRA significantly reduced the symptoms of nose scratching and sneezing, while aprepitant did not affect nasal symptoms. In the histopathological examination of the larynx, effects that would make a significant difference were found in the allergy group when compared to the control group. On the larynx, aprepitant reduced pseudostratification significantly compared to the allergy group.. Aprepitant provides histopathological changes in the treatment of allergic rhinitis, but does not have sufficient effect on nasal symptoms. The effect of aprepitant on the larynx has not been clearly demonstrated.. NA Laryngoscope, 133:2891-2897, 2023.

Topics: Animals; Aprepitant; Disease Models, Animal; Female; Histamine Antagonists; Nasal Mucosa; Neurokinin-1 Receptor Antagonists; Ovalbumin; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Substance P

The pathogenesis of allergic rhinitis (AR) is ambiguous, while it is clear that various immune cells and cytokines play crucial roles in its occurrence and development.. To investigate the effect of exogenous interleukin-10 (IL-10) on the expression of fibrinogen (FIB), procalcitonin (PCT), hypersensitive C-reactive protein (hs-CRP), and Th17/Treg-IL10/IL-17 axis balance in the nasal mucosa of rats with AR.. In this study, 48 female-specific pathogen-free Sprague-Dawley rats were randomly divided into 3 groups: blank control group, AR group, and IL-10 intervention group. The AR model was established in the AR group and IL-10 group. The rats in the control group were treated with normal saline; the rats in the AR group were given 20 μL of saline containing 50 μg of ovalbumin (OVA) every day. The rats in the IL-10 intervention group were intraperitoneally injected with 1 mL of 40 pg/kg IL-10 and provided with OVA. The IL-10 intervention group was composed of mice with AR that received IL-10. The behavior of nasal allergic symptoms (such as nasal itching, sneezing, and runny nose) and the hematoxylin and eosin staining of nasal mucosa were observed. The levels of FIB, PCT, hs-CRP, IgE, and OVA sIgE in serum were determined by enzyme-linked immunosorbent assay. The levels of Treg and Th17 cells in serum were detected by flow cytometry. The protein levels of TGF-β, IL-10, and IL-17 in nasal mucosa were detected by the Western-blot method.. The scores of snots, nasal itching, and sneezing in the AR group were significantly higher than those in the control group, while the scores of the above symptoms in the IL-10 intervention group were lower than those in the AR group. The levels of FIB, PCT, hs-CRP, IgE, and OVA sIgE in serum and the protein levels of IL-10 and IL-17 in the nasal mucosa in the AR group were higher than those in the blank control group. Meanwhile, the levels of FIB, PCT, hs-CRP, IgE, and OVA sIgE in serum and IL-10 and IL-17 protein in the nasal mucosa in the IL-10 group were lower than those in the AR group.. IL-10 can relieve the allergy of AR rats by affecting the expression of FIB, PCT, and hs-CRP, as well as the balance of the Th17/Treg-IL10/IL-17 axis in the nasal mucosa of AR rats.

Topics: Animals; C-Reactive Protein; Disease Models, Animal; Female; Fibrinogen; Hemostatics; Immunoglobulin E; Interleukin-10; Interleukin-17; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Procalcitonin; Pruritus; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Sneezing; T-Lymphocytes, Regulatory; Th17 Cells

Allergic rhinitis (AR), a chronic respiratory inflammatory disease, is among the most common chronic diseases reported worldwide. Mucus hypersecretion is a critical feature of AR pathogenesis. Although the Gleditsia sinensis extract has several beneficial effects on human health, its effects on allergic inflammation have not yet been investigated. In this study, we examined the effects of G. sinensis aqueous extract (GSAE) on nasal inflammation in an ovalbumin (OVA)-induced AR mouse model. GSAE was administered orally for 1 week and then the clinical nasal symptoms were evaluated. The levels of histamine, OVA-specific immunoglobulin (Ig) E, and interleukin (IL)-13 were measured in the serum using an enzyme-linked immunosorbent assay (ELISA). Inflammatory cells were then counted in the nasal lavage fluid (NALF) and histopathology in the nasal epithelium was evaluated. STAT3/STAT6 phosphorylation was examined in primary human nasal epithelial cells (HNEpCs) using western blot analysis. Oral administration of GSAE to OVA-induced AR mice alleviated nasal clinical symptoms and reduced OVA-specific immunoglobulin E, interleukin (IL)-13, and histamine levels. The accumulation of eosinophils in nasal lavage fluid, nasal mucosa, mast cells, goblet cells, and mucin 5AC (MUC5AC) in the nasal epithelium was also inhibited by GSAE. Treatment with GSAE inhibited the production of MUC5AC in IL-4/IL-13-stimulated primary human nasal epithelial cells through the signal transducer and activator of transcription (STAT)3/STAT6 signaling pathway. These results indicated that GSAE reduces nasal inflammation suggesting that it is a potential treatment option for AR.

Topics: Animals; Cytokines; Disease Models, Animal; Gleditsia; Histamine; Humans; Immunoglobulin E; Inflammation; Interleukin-13; Mice; Mice, Inbred BALB C; Mucin 5AC; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; STAT6 Transcription Factor

Luteolin (LO) has been reported to be a potential drug for allergic rhinitis (AR). This paper explored the mechanism of LO in AR.. The nasal sneezing frequency, nasal mucosa thickness, and levels of anti-OVA-IgE, Beclin1, LC3II/LC3I, IL-17A as well as RORγt were enhanced whereas anti-OVA-IgG2a, IL-10, and Foxp3 levels were inhibited in a mouse model of OVA-induced AR, which were reversed by LO or 3-MA treatment.. LO restored Treg/Th17 balance to ameliorate AR in a mouse model.

Topics: Animals; Beclin-1; Disease Models, Animal; Forkhead Transcription Factors; Immunoglobulin E; Immunoglobulin G; Interleukin-10; Luteolin; Mice; Mice, Inbred BALB C; Nuclear Receptor Subfamily 1, Group F, Member 3; Ovalbumin; Rhinitis, Allergic; Sneezing; T-Lymphocytes, Regulatory; Th17 Cells

An experimental rat allergic rhinitis(AR) model was made to explore the effect of different concentrations of ozone exposure and evaluate the roles of nuclear factor erythroid 2-related factor 2(Nrf2) and oxidative stress in ozone exposure.. Sprague-Dawley rats were sensitized with ovalbumin (OVA). Three groups of AR rats were exposed respectively to different concentrations of ozone for 2 h on 6 weeks. Nasal symptoms and OVA- specific Ig E in the serum were evaluated. The pathological changes in the nasal mucosa were examined. Malondialdehyde (MDA) level and activity of superoxide dismutase(SOD) and glutathione peroxidase (GSH-Px,GPX) in the nasal mucosa tissue were measured through a spectrophotometry-based method. Nrf2、Kelch-1ike ECH- associated protein-l (Keap1) proteins was measured by western blotting. GPX1、GPX2 mRNA were detected by quantitative real time-PCR(qRT-PCR).. Our results showed that ozone exposure induced a significant increase of the number of sneezes, nasal rubs, amount of nasal secretion and OVA-sIgE in the serum of AR model. Ozone effected oxidative stress in different concentration. The content of MDA in AREH group was significantly higher than AR groups. The activities of SOD and GSH-Px in nasal mucosa showed different trends in different concentration groups. The activities of SOD and GSH-Px in AREL and AREM groups were higher than AR group, but decreased at AREH group. The nucleoprotein level of Nrf2 in AREL and AREM groups was higher than AR groups. However, in AREH group, it was significantly decreased, compared with AREL and AREM groups. GPX1 and GPX2 mRNA levels in nasal mucosa showed the same trend in different exposure groups.. Different concentrations of ozone inhalation causes changes of the expression of Nrf2 nuclear protein and its target genes in nasal mucosa of AR. High concentration ozone breaks the redox balance and aggravates oxidative damage in AR. This study suggests that inhibiting oxidative stress might be a solution for ozone-elicited detrimental effects on AR.

Topics: Animals; Immunoglobulin E; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Ovalbumin; Oxidative Stress; Ozone; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic

The present study aims to investigate the effect of immunotherapy in a mouse model of allergic rhinitis (AR) and to explore the possible molecular mechanisms of action. An animal model of AR was established by sensitization and challenge of BALB/c mice with house dust mite (HDM) extract. The mice were injected subcutaneously with HDM for immunotherapy. AR nasal symptoms were evaluated according to the frequencies of nose rubbing and sneezing and the degree of rhinorrhea. The nasal mucosa and lung tissue architecture and inflammatory status by histological analysis; the infiltration of eosinophils in nasal lavage fluid (NALF) of mice was observed by Diff-Quik stain; ELISA-based quantification of serum HDM-specific IgE and TH1/TH2 cytokine concentration; and flow cytometry detected the number of serum CD4+/CD8+ cells to evaluate the mechanism of immunotherapy. It was found that after immunotherapy, the AR symptom score was reduced, the number of eosinophils in NALF was reduced, and the infiltration of inflammatory cells and tissue damage in the nasal mucosa and lung tissue were alleviated. Immunotherapy can increase the number of CD4+ T cells in the peripheral blood, increase the ratio of CD4+/CD8+ cells, increase the expression of Th1 cytokines such as IL-2 and IFN-γ, reduce the expression of Th2 cytokines such as IL-4 and IL-5. The results showed that repeated intraperitoneal injection of crude extract of HDM for sensitization, followed by nasal drops can effectively construct a mouse model of AR, and subcutaneous injection of immunotherapy in mice can reduce allergic inflammation in model mice and improve the inflammatory infiltration of the nasal cavity in allergic rhinitis. Immunotherapy can reduce the expression of inflammatory factors in AR, improve Th1/Th2 balance, and may play a role in the treatment of AR by improving the function of immune cells.

Topics: Allergens; Animals; CD4-Positive T-Lymphocytes; Cytokines; Disease Models, Animal; Immunotherapy; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Th2 Cells

Iodine-containing formulations have been widely used to treat iodine deficiency and as antiseptics. Lecithin-bound iodine (LBI) has been approved to treat allergic diseases in Japan; however, its underlying mechanism remains unknown. In this study, we show that LBI ameliorated disease symptoms in an ovalbumin (OVA)-induced allergic rhinitis mouse model. LBI suppressed OVA-specific IgE production by attenuating germinal center (GC) reaction in the draining lymph nodes. The antiallergic effect of LBI is most likely attributed to increased serum iodine levels but not thyroid hormone levels. In vitro treatment of activated B cells with potassium iodide induced ferroptosis by increasing intracellular reactive oxygen species (ROS) and ferrous iron in a concentration-dependent manner. Accordingly, LBI diets increased ROS levels in GC B cells of the draining lymph nodes. This study suggests that iodine directly promotes ferroptosis in activated B cells and attenuates GC reactions, leading to the alleviation of allergic symptoms.

Topics: Animals; Anti-Allergic Agents; Cytokines; Disease Models, Animal; Ferroptosis; Iodine; Mice; Mice, Inbred BALB C; Ovalbumin; Reactive Oxygen Species; Rhinitis, Allergic

Topics: Animals; Cell Differentiation; Cytokines; Disease Models, Animal; Immunoglobulin E; Inflammation; Interleukin-13; Interleukin-4; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Plant Extracts; Pulsatilla; Rhinitis, Allergic; STAT6 Transcription Factor; Th2 Cells

The pathogenesis of allergic rhinitis (AR)-related olfactory dysfunction (OD) remains unknown. Inhibiting microglial response in olfactory bulb (OB) can ameliorate AR-related OD, but no precise targets have been available. In this study, we established a mouse model of ovalbumin (OVA)-induced AR and combined with the application of P2X7 receptor (P2X7R)-specific antagonists and cell culture in conditioned medium to investigate the role and mechanism of OB microglial P2X7R in AR-related OD. Serum IgE and IL-5 levels determined via ELISA and federated the number of nose-scratching to affirm the success of OVA-induced AR mouse model. Buried food pellet test was used to evaluate the olfactory function of mice. The changes of IBA1, GFAP, P2X7R, IL-1β, IL-1Ra, and CASPASE 1 were detected by quantitative polymerase chain reaction and western blotting. The levels of adenosine triphosphate (ATP) were determined by the commercialized kit. The morphological changes of microglia were assessed using immunofluorescence staining and Sholl analysis. Findings showed that AR-related OD was associated with OB microglia-mediated imbalance between IL-1β and IL-1Ra. Treatment with BBG improved the olfactory function in AR mice with restoring the balance between IL-1β and IL-1Ra. In vitro, the conditioned medium obtained after HNEpC treatment with Der p1 could activate HMC3 to arise inflammatory reaction basing on "ATP-P2X7R-Caspase 1" axis, while inhibition of its P2X7R suppressed the reaction. In brief, microglial P2X7R in OB is a direct effector molecule in AR-related OD and inhibition of it may be a new strategy for the treatment of AR-related OD.

Topics: Adenosine Triphosphate; Animals; Caspase 1; Culture Media, Conditioned; Disease Models, Animal; Interleukin 1 Receptor Antagonist Protein; Mice; Microglia; Olfaction Disorders; Olfactory Bulb; Ovalbumin; Receptors, Purinergic P2X7; Rhinitis, Allergic

Particulate matter (PM) is a major component of air pollution from emissions from anthropogenic and natural sources and is a serious problem worldwide due to its adverse effects on human health. Increased particulate air pollution increases respiratory disease-related mortality and morbidity. However, the impact of PM with an aerodynamic diameter of ≤ 2.5 μm (PM2.5) on combined allergic rhinitis and asthma syndrome (CARAS) remains to be elucidated. Accordingly, in the present study, we investigated the effect of PM2.5 in an ovalbumin (OVA)-induced CARAS mouse model with a focus on NF-κB signaling.. We established an OVA-induced mouse model of CARAS to determine the effects of exposure to PM2.5. BALB/c mice were randomly divided into four groups: (1) naive, (2) PM2.5, (3) CARAS, and (4) CARAS/PM2.5. Mice were systemically sensitized with OVA and challenged with inhalation of ultrasonically nebulized 5% OVA three times by intranasal instillation of OVA in each nostril for 7 consecutive days. Mice in the PM2.5 and CARAS/PM2.5 groups were then exposed to PM2.5 by intranasal instillation of PM2.5 for several days. We then examined the impacts of PM2.5 exposure on histopathology and NF-κB signaling in our OVA-induced CARAS mouse model.. Our results demonstrate that PM2.5 can aggravate OVA-induced CARAS.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Humans; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; Particulate Matter; Rhinitis, Allergic; Signal Transduction

Allergic rhinitis (AR) is a common atopic problem in which immune response to the environmental factors leads to clinical symptoms.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Immunoglobulin E; Interleukin-33; Interleukin-4; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Th2 Cells

Allergic reaction is the most common nasal conditions worldwide and it will remain throughout life. The symptoms of an allergic reaction include sneezing, itching, hives, swelling, difficulty breathing, and a runny nose. Hydroxysafflor yellow A (HYA) is a flavonoid compound which is the active phyto-constituent of flower of Carthamus tinctorius L., and exhibited the various medicinal activities like antioxidant, anti-inflammatory and cardiovascular protective effects. This study aimed to assess the efficacy and mode of action of HYA against the allergic rhinitis induced by ovalbumin in mice. HYA was given orally to the Swiss BALB/s mice once daily, 1 h before, they were challenged with ovalbumin (OVA) via intranasal administration, after that the mice were sensitized via intraperitoneal injection of OVA. Allergic nasal symptoms, body weight, spleen weight, OVA-specific immunoglobulins, inflammatory cytokines, Th17 cytokines and Th17 transcription factors also estimated. HYA had a significant (p < .001) effect on body weight and reduced spleen weight. It effectively decreased the nasal symptoms of allergy such as sneezing, rubbing, and redness. HYA significantly reduced the level of malonaldehyde (MDA) and improved levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione (GSH). It also remarkably decreased the levels of Th2 cytokines and Th17 transcription factors like RAR-related orphan receptor gamma (ROR-γ), signal transducer and activator of transcription 3 (STAT3) and phosphor signal transducer and activator of transcription 3 (p-STAT3), while increasing levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). The treatment with HYA improved the lung histology in mice with allergic rhinitis. The results suggest that HYA may have therapeutic potential against ovalbumin-induced allergic rhinitis in mice, by altering the Th17/Treg balance and improving the Nrf2/HO-1 signaling pathway.

Topics: Animals; Body Weight; Cytokines; Disease Models, Animal; Heme Oxygenase-1; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-E2-Related Factor 2; Ovalbumin; Rhinitis, Allergic; Signal Transduction; Sneezing; STAT3 Transcription Factor

Although M2 macrophages are involved in the orchestration of type 2 inflammation in allergic diseases, the mechanisms underlying non-coding RNA (ncRNA)-mediated macrophage polarization in allergic rhinitis (AR) have not been systematically understood. Here, we identified long non-coding RNA (lncRNA) MIR222HG as a key regulator of macrophage polarization and revealed its role in AR. Consistent with our bioinformatic analysis of GSE165934 dataset derived from the Gene Expression Omnibus (GEO) database, lncRNA-MIR222HG and murine mir222hg were downregulated in our clinical samples and animal models of AR, respectively. Mir222hg was upregulated in M1 macrophages and downregulated in M2 macrophages. The allergen-ovalbumin facilitated polarization of RAW264.7 cells to the M2 phenotype, accompanied by the downregulation of mir222hg expression in a dose-dependent manner. Mir222hg facilitates macrophage M1 polarization and reverses M2 polarization caused by ovalbumin. Furthermore, mir222hg attenuates macrophage M2 polarization and allergic inflammation in the AR mouse model. Mechanistically, a series of gain- and loss-of-function experiments and rescue experiments were performed to verify the role of mir222hg as a ceRNA sponge that adsorbed miR146a-5p, upregulated Traf6, and activated the IKK/IκB/P65 pathway. Collectively, the data highlight the remarkable role of MIR222HG in the modulation of macrophage polarization and allergic inflammation, as well as its potential role as a novel AR biomarker or therapeutic target.

Topics: Animals; Inflammation; Macrophages; Mice; NF-kappa B; Ovalbumin; RAW 264.7 Cells; Rhinitis, Allergic; RNA, Long Noncoding; TNF Receptor-Associated Factor 6

Allergic rhinitis (AR) is resulted from immunoglobulin E (IgE)-mediated reactions to inhaled allergens which elicit mucosal inflammation and impair epithelial barrier integrity. However, whether miR-29a-3p as an epigenetic regulator that can contribute to epithelial barrier dysfunction in the pathogenesis of AR, and its underlying mechanism remians unclear. In this study, we discovered that miR-29a-3p was upregulated in AR patients and preferentially expressed in epithelial and glandular cells of nasal mucosa. VCL and CTNNB1, candidate target genes of miR-29a-3p, were predicted with several databases, including miRDB, miRanda, microT-CDS and TargetScan, and were validated through dual-luciferase reporter assay system. These two proteins were strongly associated with adherens junction (AJ) and tight junction (TJ) of nasal mucosa epithelial cells, in which played vital roles in mucosal integrity and nasal epithelial barrier function stability. Results for HNEpC culture and in vitro treatment experiments showed that expression of VCL and CTNNB1 were inhibited by miR-29a-3p mimic and were enhanced by miR-29a-3p inhibitor. In OVA-induced AR mice model, the expression pattern of miR-29a-3p and its target genes (Vcl and Ctnnb1) were consistent with the aforementioned quantitative results in AR patients, and miR-29a-3p antagomir could partially alleviate the symptom of OVA-induced AR in mice, restoring mucosal integrity and paracellular barrier function. In conclusion, our findings indicate that miR-29a-3p targets CTNNB1 and VCL to regulate nasal epithelial permeability and barrier function integrity, which may serve as a potential novel therapeutic target for the treatment of AR.

Topics: Animals; Mice; MicroRNAs; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic

Combined allergic rhinitis and asthma syndrome (CARAS) causes chronic respiratory inflammation in allergic individuals. Long-term exposure to particulate matter 2.5 (PM2.5; particles 2.5 µm or less in diameter) can aggravate respiratory damage. Bergapten (5-methoxysporalen) is a furocoumarin mostly found in bergamot essential oil and has significant antioxidant, anticancer, and anti-inflammatory activity. This study created a model in which CARAS was exacerbated by PM2.5 exposure, in BALB/c mice and explored the potential of bergapten as a therapeutic agent. The bergapten medication increased ovalbumin (OVA)-specific immunoglobulin (Ig) G2a level in serum and decreased OVA-specific IgE and IgG1 expression. Clinical nasal symptoms diminished significantly, with weakened inflammatory reaction in both the nasal mucosa and lungs. Furthermore, bergapten controlled the T helper (Th)1 to Th2 ratio by increasing cytokines associated with Th1-like interleukin (IL)-12 and interferon gamma and decreasing the Th2 cytokines IL-4, IL-5, and IL-13. Factors closely related to the balance between regulatory T cells and Th17 (such as IL-10, IL-17, Forkhead box protein P3, and retinoic-related orphan receptor gamma) were also regulated. Notably, pro-inflammatory cytokines IL-6, IL-1β, and tumor necrosis factor-alpha were reduced by bergapten, which suppressed the activation of both the signal transducer and activator of transcription 3 signaling pathway and the mitogen-activated protein kinase signaling pathway. Therefore, bergapten might have potential as a therapeutic agent for CARAS.

Topics: 5-Methoxypsoralen; Animals; Asthma; Cytokines; Disease Models, Animal; Inflammation; Mice; Mice, Inbred BALB C; Ovalbumin; Particulate Matter; Rhinitis, Allergic; STAT3 Transcription Factor; T-Lymphocytes, Regulatory

Mast cells (MCs) are important therapeutic targets for allergic diseases. High-affinity immunoglobulin E (IgE) Fc receptors (FcεRI) trigger abnormal activation of MCs. Allergic rhinitis (AR) is an IgE-mediated antigen inhalation reaction that occurs in the nasal mucosa. MC aggravation and dysfunction were observed during the early stages of AR pathogenesis. Herb-derived dictamnine exhibits anti-inflammatory effects. Here, we investigated the pharmacological effects of herb-derived dictamnine on IgE-induced activation of MCs and an ovalbumin (OVA)-induced murine AR model. The results indicated that dictamnine attenuated OVA-induced local allergic reactions and reduced body temperature in OVA-challenged mice with active systemic anaphylaxis. Additionally, dictamnine decreased the frequency of nasal rubbing and sneezing in an OVA-induced murine AR model. Moreover, dictamnine inhibited FcεRI-activated MC activation in a dose-dependent manner without causing cytotoxicity, reduced the activation of the tyrosine kinase LYN in LAD2 cells, and downregulated the phosphorylation of PLCγ1, IP3R, PKC, Erk1/2, and Akt, which are downstream of LYN. In conclusion, dictamnine suppressed the OVA-stimulated murine model of AR and activated IgE-induced MCs via the LYN kinase-mediated molecular signaling pathway, suggesting that dictamnine may be a promising treatment for AR.

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Signal Transduction

Allergic rhinitis (AR) is a nasal mucosal disease with sneezing and nasal itching as the main symptoms. Although AR treatment continues to improve, there remains a lack of effective drugs. There are still controversies regarding whether anticholinergic drugs can effectively and safely relieve the symptoms of AR and reduce inflammation in the nasal mucosa. Here, we synthesized 101BHG-D01, which is a novel anticholinergic drug that mainly targets the M3 receptor and may reduce the adverse effects of other anticholinergic drugs on the heart. We evaluated the effects of 101BHG-D01 on AR and investigated the potential molecular mechanism of anticholinergic therapy for AR. We found that 101BHG-D01 effectively alleviated AR symptoms, reduced the infiltration of inflammatory cells and attenuated the expression of inflammatory factors (IL-4, IL-5, IL-13, etc.) in various AR animal models. In addition, 101BHG-D01 reduced the activation of mast cells and the release of histamine from rat peritoneal mesothelial cells (RPMCs) challenged by IgE. Moreover, 101BHG-D01 reduced the expression of MUC5AC in IL-13-challenged rat nasal epithelial cells (RNECs) and human nasal epithelial cells (HNEpCs). Furthermore, IL-13 stimulation significantly increased JAK1 and STAT6 phosphorylation, which was suppressed by 101BHG-D01. We demonstrated that 101BHG-D01 reduced mucus secretion and inflammatory cell infiltration in the nasal mucosa, which may occur through a reduction in activation of the JAK1-STAT6 signaling pathway, indicating that 101BHG-D01 is a potent and safe anticholinergic therapy for AR.

Topics: Animals; Cytokines; Disease Models, Animal; Humans; Immunoglobulin E; Interleukin-13; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rats; Rhinitis, Allergic

Allergic rhinitis (AR) is a common allergic disease characterized by nasal congestion, rhinorrhoea, and sneezing. Cineole, a monoterpenoid compound widely present in various volatile oils, has a wide range of pharmacological activities and is of interest in allergic airway diseases for its anti-inflammatory and anti-mucus production abilities. However, the protective effects of cineole in mice with allergic rhinitis and its mechanisms have not been well investigated. In this study, the protective effect of cineole against ovalbumin-induced (OVA-induced) allergic rhinitis and its molecular mechanism is investigated by metabolomic analysis based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). OVA combined with aluminum hydroxide adjuvant is used to sensitize and establish the allergic rhinitis (AR) mouse model. The mice are randomly divided into groups of control, AR, cineole (30 mg/kg), and budesonide (38.83 μg/kg). The pharmacodynamic results show that cineole significantly reduces the levels of Th2-type cytokines and OVA-specific IgE (OVA-sIgE) in AR mice, improves nasal mucosal tissue damage and alleviates nasal symptoms compared to the untreated AR group. Metabolomic results show that arachidonic acid (AA) metabolism and tryptophan (Trp) metabolism are reprogrammed on the basis of 27 significantly altered metabolites. Further studies show that cineole inhibits the biosynthesis of pro-inflammatory lipid mediators leukotrienes (LTs) and prostaglandins (PGs) in mice by inhibiting the activity of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) in the arachidonic acid metabolic (AA metabolic) pathway. It also inhibits the production of Th2 cytokines and inflammatory cell infiltration, thereby alleviating symptoms such as nasal congestion and nasal leakage. These results reveal the action and molecular mechanism of cineole in alleviating AR and provide a theoretical basis for the clinical application of cineole in treating AR.

Topics: Animals; Arachidonic Acid; Chromatography, Liquid; Cytokines; Disease Models, Animal; Eucalyptol; Immunoglobulin E; Leukotrienes; Metabolomics; Mice; Mice, Inbred BALB C; Ovalbumin; Prostaglandins; Rhinitis, Allergic; Tandem Mass Spectrometry

Neurokinin-1 receptor (NK-1R) and normal T cell expressed and secreted (RANTES) have been shown to play important roles in allergic rhinitis (AR). However, whether the regulating effect of NK-1R in AR is achieved via RANTES remains unknown.. In the present study, Sprague-Dawley rats were sensitized and challenged with ovalbumin to make AR models. During the challenge period, the rats were treated intranasally with NK-1R-specific small interfering RNA (siRNA) for NKR group, negative siRNA for NCS group, rats in NSAR group and NS group were given saline. The amount of nasal secretion and the numbers of nose rubs and sneezes were measured in each rat. The levels of NK-1R and RANTES in the nasal mucosal tissues were determined through real-time fluorescence quantitative RT-PCR and immunohistochemical staining. The numbers of eosinophils in the collected nasal lavage fluid (NLF) were counted, and the concentration of RANTES in NLF was determined by enzyme-linked immunosorbent assay.. Compared with that in the NS group, the expression of NK-1R and RANTES was significantly higher in the nasal mucosa of NSAR and NCS group rats. The sneezing and nose rubbing counts and the amount of nasal secretions were increased significantly in the NSAR and NCS groups. Rats in the NKR group experienced greater relief from AR symptoms than rats in the NSAR and NCS groups. Furthermore, knockdown of NK-1R expression also significantly eliminated RANTES expression and eosinophil infiltration in the nasal mucosa of NKR group rats.. For the first time, we show that intranasal treatment with NK-1R-specific siRNA can significantly decrease RANTES expression, AR-related symptoms, and eosinophil inflammation, suggesting that the regulating effect of NK-1R in the development of AR occurs via alteration of RANTES expression.

Topics: Animals; Chemokine CCL5; Disease Models, Animal; Gene Knockdown Techniques; Nasal Mucosa; Ovalbumin; Rats; Rats, Sprague-Dawley; Receptors, Neurokinin-1; Rhinitis, Allergic; RNA, Small Interfering; Sneezing

Combined allergic rhinitis and asthma syndrome (CARAS) is an allergic airway inflammatory disorder orchestrated by the type 2 immune response. The close gut-lung relationship has been described, however, the effect of gut-modulating agents such as probiotics in allergic airway disorder is unclear. Thus, the goal of this study was to evaluate theLimosilactobacillus fermentumsupplementation in animals with CARAS. Therefore, BALB/c mice were ovalbumin (OVA) -sensitized and -challenged after being supplemented withL. fermentum. Animals, previously probiotic supplemented, showed a decrease (p < 0.05) of inflammatory cell migration, mainly eosinophil, into the nasal (NALF) and the bronchoalveolar (BALF) fluids as well as reduction of the allergic signs such as sneezing, nasal rubbings, and nasal hyperreactivity induced by histamine as compared with non-supplemented animals. In the systemic context,L. fermentumreduced eosinophilia and the serum levels of OVA-specific IgE. The altered histological aspects of nasal and lung tissues of animals with CARAS were effectively ameliorated byL. fermentum. In the BALF, the immunomodulatory effect was due to the decreasing of type 2 and 3 cytokines (IL-4, IL-13, IL-5 and IL-17A) dependent on type 1 (IFN-γ) and Treg (IL-10) cytokine increasing. Indeed,L. fermentumimproved the FOXP3 activation. Additionally, these effects correlate with the amplification of the gut response as increasing short-chain fatty acids (SCFAs) levels, gut epithelium barrier (ZO-1) maintenance, and colon tissue integrity. These data pointed out that animals' probiotic supplemented presented immunomodulatory responses in CARAS experimental model by activating the intracellular transduction signal underlying the IL-10 gene transcription.

Topics: Allergens; Animals; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Forkhead Transcription Factors; Immunity; Interleukin-10; Limosilactobacillus fermentum; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Fallopia japonica; Inflammation; Interleukin-33; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Signal Transduction

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa that is mediated by immunoglobulin E (IgE). Xiao-qing-long-tang (XQLT) is a traditional Chinese medicine compound that is widely used to treat respiratory diseases such as AR. However, the underlying mechanism of the effect of XQLT on AR remains unclear.. To elucidate the effect of XQLT on ovalbumin (OVA)-induced AR and the mechanisms of action.. The therapeutic efficacy of XQLT was evaluated in a well-established OVA-induced AR mouse model. Nasal symptoms were analyzed, type 2 cytokines and OVA-sIgE levels were measured, nasal mucosa tissues were collected for histological analysis, and the changes of Group 2 innate lymphoid cells (ILC2s) and the IL-33/ST2 and JAK/STAT signaling pathways in the nasal mucosa were observed.. XQLT significantly alleviated the nasal symptoms and histological damage to the nasal mucosa in AR mice, and reduced the levels of type 2 cytokines and OVA-sIgE. In addition, after XQLT treatment, the numbers of ILC2s in the nasal mucosa of AR mice were reduced, and the mRNA levels of the transcription factors GATA3 and ROR-α were decreased. Moreover, IL-33/ST2 signaling pathway was inhibited. The costimulatory cytokine associated JAK/STAT signaling pathway was also inhibited in ILC2s.. Our study demonstrated that XQLT regulated ILC2s through the IL-33/ST2 and JAK/STAT pathways to ameliorate type 2 inflammation in OVA-induced AR. These findings suggest that XQLT might be used to treat AR.

Topics: Animals; Cytokines; Disease Models, Animal; Immunity, Innate; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Janus Kinases; Lymphocytes; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Signal Transduction; STAT Transcription Factors

Allergic rhinitis (AR) remains a frequent aspiratory allergic inflammatory disorder with a high incidence. Circular RNAs (circRNAs) have been revealed to participate in the pathogenesis of AR. This study investigated the biological function of circMIRLET7BHG (hsa_circ_0008668) in AR progression.. Ovalbumin (OVA)-exposed human nasal epithelial cell line (HNEpC) and mice were adopted as the in vitro and in vivo models of AR. Immunofluorescence staining was used to determine epithelial tight junction protein expression. Target molecule levels were assessed by RT-qPCR and Western blotting. Localization of circMIRLET7BHG and IGF2BP1 was observed by RNA-FISH and immunofluorescence. Epithelial barrier damage was determined by transepithelial electrical resistance and fluorescein isothiocyanate-dextran (FD4) permeability. Serum concentrations of IgE, sIgE, IFN-γ, IL-4, and IL-5 were detected by ELISA. Apoptosis, pathological changes, and eosinophil infiltration in nasal mucosa tissues were evaluated by TUNEL, H&E, and Sirius red staining, respectively. Molecular mechanism was analyzed by RNA pull-down, RIP, and MeRIP assays.. An increased expression of circMIRLET7BHG was found in AR patients and experimental models. Down-regulation of circMIRLET7BHG attenuated OVA-induced allergic symptoms via relieving epithelial thicknesses, eosinophil infiltration, apoptosis, and inflammatory response in mice. Subsequently, circMIRLET7BHG deficiency prevented OVA-induced epithelial barrier dysfunction by reducing epithelial permeability, and inhibiting tight junction proteins. Mechanistically, methyltransferase-like 3 (METTL3) enhanced circMIRLET7BHG expression via m6A methylation, which enhanced ADAM10 mRNA stability via interaction with IGF2BP1.. METTL3-mediated m6A modification increased circMIRLET7BHG expression that consequently raised ADAM10 mRNA stability via interplay with IGF2BP1, thereby promoting AR by inducing epithelial barrier dysfunction.

Topics: ADAM10 Protein; Animals; Humans; Methyltransferases; Mice; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; RNA

Allergic rhinitis (AR) is an inflammatory disorder of the nasal mucosa, and is a worldwide health problem with a significant impact on the quality of life. The main goal of AR treatment is to relieve symptoms. However, standard treatments have considerable side effects or are not effective. Photobiomodulation (PBM) therapy has emerged as an alternative treatment. Here, we evaluated the effects of transcutaneous systemic (tail) or local (skin over nostrils) PBM using a 660-nm light-emitting diode (LED) array. Adult rats were assigned into 4 groups: basal, as non-manipulated animals; Sham, as rats sensitized with 7 intradermal injections of ovalbumin (OVA) plus alum followed by intranasal instillation with OVA (2%) daily for 7 days; and the LPBM and SPBM groups, in which the animals were treated with PBM (local or systemic) immediately after the last instillation of OVA (1%) daily for 3 days. Our results showed that local PBM treatment reduced mast cell degranulation in the nasopharynx and nostrils; levels of leukotriene B4, thromboxane A2, and interleukin 4 (IL-4) in the nasopharynx; and gene expression of IL-4. Moreover, we showed higher levels and gene expression of IL-10 after local PBM treatment. Systemic PBM treatment did not change any of the evaluated parameters. In conclusion, our data showed that local (but not systemic) treatment with PBM could improve parameters related to AR in an animal model, and should be tested clinically.

Topics: Animals; Cell Degranulation; Cytokines; Disease Models, Animal; Eicosanoids; Mice; Mice, Inbred BALB C; Ovalbumin; Quality of Life; Rats; Rhinitis, Allergic

Low-level light therapy (LLLT) is widely used for the photobiomodulation of cell behavior. Recent studies have shown that LLLT affects the proliferation and migration of various types of mesenchymal stem cells (MSCs). However, there is a lack of studies investigating the effect of LLT on enhancing the immunomodulatory properties of tonsil-derived MSCs (T-MSCs).. The aim of this study was to investigate the immunomodulatory effects of conditioned media from T-MSCs (T-MSCs-CM) treated with LLLT in allergic inflammation.. We isolated T-MSCs from human palatine tonsils and evaluated the ingredients of T-MSCs-CM. The effect of T-MSCs-CM treated with LLLT was evaluated in a mouse model of allergic rhinitis (AR). We randomly divided the mice into four groups (negative control, positive control, T-MSCs-CM alone, and T-MSCs-CM treated with LLLT). To elucidate the therapeutic effect, we assessed rhinitis symptoms, serum immunoglobulin (Ig), the number of inflammatory cells, and cytokine expression.. We identified increased expression of immunomodulatory factors, such as HGF, TGF-β, and PGE, in T-MSCs-CM treated with LLLT, compared to T-MSCs-CM without LLLT. Our animal study demonstrated reduced allergic symptoms and lower expression of total IgE and OVA-specific IgE in the LLLT-treated T-MSCs-CM group compared to the AR group and T-MSCs-CM alone. Moreover, we found that T-MSCs-CM treated with LLLT showed significantly decreased infiltration of eosinophils, neutrophils, and IL-17 cells in the nasal mucosa and reduced IL-4, IL-17, and IFN-γ expression in OVA-incubated splenocytes compared to the AR group.. The present study suggests that T-MSCs-CM treated with LLLT may provide an improved therapeutic effect against nasal allergic inflammation than T-MSCs-CM alone.

Topics: Animals; Anti-Allergic Agents; Cytokines; Disease Models, Animal; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Palatine Tonsil; Rhinitis, Allergic; Secretome

Shin'iseihaito (Xinyiqingfeitang) is a formula of traditional Japanese Kampo medicine and traditional Chinese medicine (TCM) and for chronic sinusitis. However, the precise action mechanism has been unknown. We examined the effect of shin'iseihaito extract (SSHT) on murine allergic rhinitis model using ovalbumin (OVA). We decocted the mixture of 9 crude drugs in water to prepare SSHT. SSHT (20 times amount of human dose) was orally administered to mice treated with OVA. After mice were sacrificed on day 28, immunoglobulin (Ig) E, interleukin (IL)-4, IL-13, interferon (IFN)-γ, and thymic stromal lymphopoietin (TSLP) levels in nasal lavage fluid samples were measured by enzyme-linked immunosorbent assay (ELISA). The pathological tissue sections from the nasal epithelial mucosa were histopathologically investigated by optical and scanning electron microscopies. We also investigated the effects of modified SSHTs prepared by removing one crude drug from shin'iseihaito to clarify the active ingredients. SSHT suppressed IgE, IL-4, IL-13, and TSLP levels, while increased the IFN-γ levels in OVA-induced allergic mice. Sensitization with OVA resulted in an increase in eosinophilia and goblet cells in murine nasal cavity tissue in comparison with those in untreated group, however, those were significantly reduced by the treatment with SSHT. The extracts of 8 crude drug's mixtures except for the removal of Gypsum fibrosum (GF) from shin'iseihaito counteracted on the suppressive effects of SSHT on IgE, IL-4, IL-13, and TSLP levels in nasal lavage fluid. Our result demonstrated that SSHT may contribute to inhibit the exacerbation of OVA-induced murine allergic rhinitis by regulating cytokines, and the components except for GF contributed anti-allergic effect of shin'iseihaito.

Topics: Animals; Cytokines; Disease Models, Animal; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Plant Extracts; Rhinitis, Allergic

Allergic rhinitis (AR) is one of the most common allergic inflammatory diseases worldwide. In AR, increased blood flow and vascular permeability in nasal mucosa cause rhinorrhea and nasal congestion. We investigated the role of an 11Z,14Z-eicosadienoic acid-derived metabolite, 15-hydroxy-11Z,13Z-eicosadienoic acid (15-HEDE), in functional changes in vasculature and nasal congestion in AR. Repeated intranasal administration of Ovalbumin (OVA) caused AR symptoms, such as sneezing and nasal congestion, in mice. OVA administration increased the level of 15-HEDE in nasal lavage fluid, which reached approximately 0.6 ng/ml after ten OVA treatments. Upon measuring vascular contraction, treatment with 0.1-3 μM 15-HEDE did not cause contraction in mouse aortae, while it dilated aortae that were pre-contracted by thromboxane receptor stimulation. Pretreatment with the voltage-gated K

Topics: Administration, Intranasal; Animals; Disease Models, Animal; Eicosanoic Acids; Human Umbilical Vein Endothelial Cells; Humans; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic

Abatacept (Aba) is a cytotoxic T-lymphocyte antigen-4 and fragment crystallizable fusion protein. Aba blocks B7/Cluster of differentiation 28 - cytotoxic T-lymphocyte antigen-4 costimulatory pathway, inhibits cluster of differentiation 4. We conducted this study to assess the effectiveness of Aba in the treatment of allergic rhinitis (AR) in a mouse model.. We divided 40 four-week-old BALB/c mice into four groups: control group (. Symptoms of AR significantly improved in the AR + Aba and AR + Dex groups compared with the AR group. Fewer eosinophils and goblet cells were seen in the AR + Aba and AR + Dex groups compared with the AR group. Both the AR + Aba and AR + Dex groups showed a significant decrease in nasal T helper 2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13 and T cell activation related IL-17A, and interferon gamma (IFN- γ). Total immunoglobulin (Ig) E and OVA-specific IgG1 levels were also significantly lower in the AR + Aba and AR + Dex groups. OVA-specific IgE level was also significantly lower in the AR + Aba than AR group.. Aba suppresses allergic inflammation and appears to be a good treatment for AR.

Topics: Abatacept; Animals; CTLA-4 Antigen; Cytokines; Disease Models, Animal; Immunoglobulin E; Inflammation; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic

The present study aims to investigate the effects of CCR3 gene knockout in bone marrow cells (CCR3-KO) on the mouse model of combined allergic rhinitis and asthma syndrome (CARAS). It was found that CCR3-KO significantly reduced eosinophil (EOS) migration into the nasal (NALF) and bronchoalveolar (BALF) cavities of mice, and decreased Th2 cytokines (such as, IL-4, IL-5 and IL-13) levels in nasal mucosa and lung tissues. In addition, histological analysis showed that the damage degree of nasal mucosa structure in ovalbumin (OVA) modulated CCR3-KO mice was significantly less than that in OVA modulated Wild type (WT) mice, with reduced inflammatory cell infiltration and nasal mucus secretion. The infiltration of inflammatory cells in lung tissue was significantly reduced, and the proliferation of lung smooth muscle layer and extracellular matrix (ECM) production were decreased. Symptom analysis showed that CCR3-KO can reduced allergic rhinitis (AR) signals as nose scratching and sneezing. It was also found CCR3-KO reduce OVA-induced weight loss. The results showed that CCR3-KO could reduce the symptoms of allergic inflammation in CARAS mice by reducing airway inflammatory cell infiltration and down-regulating the expression of Th2 cytokines, and CCR3 gene could be used as a target gene for the treatment of CARAS.

Topics: Allergens; Animals; Asthma; Bone Marrow Cells; Bronchoalveolar Lavage Fluid; Cytokines; Eosinophils; Immunoglobulin E; Lung; Mice, Inbred C57BL; Mice, Knockout; Nasal Lavage Fluid; Nasal Mucosa; Ovalbumin; Receptors, CCR3; Rhinitis, Allergic; Syndrome; Th2 Cells

This study was designed to evaluate the effects of BoxA on allergic rhinitis (AR). Ovalbumin (OVA)-induced AR mice model was employed and BoxA was administered to AR mice. AR symptoms, levels of cytokines and chemokines, and the expression of high mobility group box 1 (HMGB1), TLR2, and TLR4 were measured. BoxA treatment significantly ameliorated AR symptoms, decreased level of histamine, OVA-specific antibodies, suppressed the infiltration of immune cells in nasal tissues, inhibited the expression of IL-4, IL-6, IL-5, TNF-α, IL-13, IL-17, IL-2 while promoting the expression of IL-10, suppressed the expression of HMGB1, TLR2, and TLR4 in AR mice. BoxA ameliorated allergic rhinitis in mice by inhibiting HMGB1.

Topics: Animals; Cytokines; Disease Models, Animal; HMGB1 Protein; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic

Allergic rhinitis (AR) is a chronic inflammatory disorder associated with a high prevalence of anxiety symptoms and respiratory disorders that adversely affect the quality of life. Studies have shown that allergen exposure induces anxiety-like behaviors. On the other hand, stress impairs the breathing pattern. However, the effect of stress on respiration and the relationship between anxiety-like behavior and stress-induced changes in breathing pattern has not been evaluated in AR. We assessed the impact of ovalbumin (OVA)-induced anxiety-like behaviors on stress-induced breathing pattern changes. Our findings showed that the allergic rhinitis induced by OVA challenge in sensitized rats induces anxiety-like behavior. Also, we found that stress decreases respiratory irregularity and increases respiratory variability, as well as the synchronization between IBI and RV time-series in AR animals. Moreover, in AR animals, we found a significant positive correlation between anxiety-like behavior and respiratory irregularity under non-stress conditions. Besides, a significant negative correlation was observed under stress conditions. The findings showed that anxiety-related behaviors may contribute to respiratory impairments under stress conditions in AR.

Topics: Allergens; Animals; Anxiety; Behavior, Animal; Disease Models, Animal; Ovalbumin; Rats; Respiratory Rate; Rhinitis, Allergic; Stress, Psychological

Flos Magnoliae (the dried flower buds of Magnolia biondii Pamp, FM) is a known herbal traditional medicine used for the symptomatic relief of nasal congestion and rhinorrhea caused by rhinitis and sinusitis. Magnolol, a neolignan from the magnolia family, is a secondary metabolite known to have anti-allergic and anti-inflammatory effects. However, the underlying mechanisms and therapeutic effect of magnolol in the treatment of allergic rhinitis (AR) remain elusive.. Anoctamin 1 (ANO1), a calcium-activated anion channel, mediates mucus and electrolyte secretion in nasal airway epithelial cells, whereas calcium release-activated calcium channel protein 1 (ORAI1) participates in the activation of T-lymphocytes and mast cells. The aim of our study is to understand the mechanisms of action of magnolol against AR, i.e., whether it acts through the modulation of ANO1 and ORAI1 channels that are expressed in nasal epithelial cells and T-lymphocytes, respectively.. Whole-cell patch clamp was used to record the activity of ORAI1 and ANO1 ion channels in ORAI1 or ANO1 overexpressed HEK293T cells, while the Ussing chamber apparatus was used to measure electrolyte transport via the epithelium, in Calu-3 cells cultured in an air-liquid interface. Additionally, calcium imaging of Jurkat T-lymphocytes was used to assess changes in the intracellular calcium concentration. Magnolol toxicity was assessed using the CCK-8 assay, and its effect on T-lymphocyte proliferation was measured by labeling human primary T-lymphocytes with carboxyfluorescein succinimidyl ester. Finally, OVA-induced Balb/c mice were employed to evaluate the effect of magnolol on nasal symptoms, as well as cytokine and eosinophil infiltration in AR.. Magnolol inhibits ORAI1 and ANO1 channels in a concentration-dependent manner. Magnolol (30 μM) inhibits anti-CD3 induced cellular proliferation and production of IL-2 via ORAI1 channels in T-lymphocytes. Further, ATP-induced electrolyte transport mediated by ANO1 channels is significantly inhibited by magnolol in IL-4 sensitized Calu-3 cells. Notably, 300 μM magnolol significantly attenuates cytokine and eosinophil infiltration, thus alleviating AR symptoms in mice OVA-induced AR.. Magnolol may be a promising therapeutic agent for the treatment and prevention of AR.

Topics: Animals; Anoctamin-1; Anti-Allergic Agents; Biphenyl Compounds; Cell Line, Tumor; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Flowers; HEK293 Cells; Humans; Lignans; Magnolia; Mice; Mice, Inbred BALB C; Neoplasm Proteins; ORAI1 Protein; Ovalbumin; Patch-Clamp Techniques; Rhinitis, Allergic

Studies have shown that tanshinone IIA (TIIA) has an anti-inflammatory effect, but the effect on allergic rhinitis (AR) is unclear.. In this study, we explore the effect of TIIA on AR.. AR mice model was established by the intraperitoneal (ip) injection of 50 μg ovalbumin (OVA). AR mice in the dose tested groups were treated with TIIA (10 mg/kg/d, ip) or dexamethasone (Dex) (2.5 mg/kg/d, oral). The number of nasal rubbing in mice was counted. Inflammatory, goblet and mast cells in nasal mucosal tissue were detected. The contents of histamine, OVA-immunoglobulin E (IgE), OVA-immunoglobulin G1 (IgG1), tumour necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-5, interferon-γ (IFN-γ) and IL-12 in nasal lavage fluid (NALF) or serum were measured. Human mast cells (HMC-1) were treated with C48/80 to release histamine or TIIA for therapeutic effect, and the cell viability, histamine content and mast cell degranulation were examined.. TIIA alleviates OVA-induced AR symptoms in AR mice, and may be applied as a therapeutic drug for patients with Th2-, or mast cell-allergic disorders.

Topics: Abietanes; Animals; Anti-Inflammatory Agents; Cytokines; Dexamethasone; Disease Models, Animal; Histamine Release; Male; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Th2 Cells

Allergic rhinitis (AR), a major chronic inflammatory disease of the respiratory system, is a public health issue because of its substantial negative impact on quality of life and work efficiency alongside its high prevalence and costs. Dapsone is a sulfone chemical with reported anti-inflammatory and antibacterial properties. Accordingly, we investigated the anti-inflammatory impact of dapsone on ovalbumin-induced allergic rhinitis in balb/c mice.. Intraperitoneal ovalbumin and hydroxide aluminum injection followed by intranasal ovalbumin administration sensitized female Balb/c mice. Mice received intraperitoneal dapsone either acute (5, 10, 20 mg/kg) 30 min before the last ovalbumin challenge, or chronic (20 mg/kg) on days 21 to 35.. Both acute and chronic intraperitoneal usage of dapsone showed a considerable decrease in the nasal scratching behavior, the number of sneezing, serum IL-4 and IgE levels of ovalbumin-induced AR in balb/c mice, but there was a significant increase in serum IFNγ level. Histopathological analysis demonstrated a significant reduction of eosinophil numbers, following dapsone injection. Goblet cell hyperplasia and respiratory epithelial-thickness decreased significantly in the acute and chronic 20 mg/kg dapsone groups compared to the ovalbumin-induced controls.. This study shows that there is an association between acute and chronic dapsone treatment and some anti-allergic effects through an inflammation cascade.

Topics: Animals; Cytokines; Dapsone; Disease Models, Animal; Female; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Quality of Life; Rhinitis, Allergic

Fructus Amomi Cardamomi (FA) is the mature fruit of Amomum villosum Lour (family Zingiberaceae) and is commonly used in Chinese traditional medicine to treat various gastrointestinal disorders. FA's possible benefits as an allergic rhinitis (AR) treatment, however, have not been examined. We used an ovalbumin (OVA)-induced AR mouse model to identify any anti-allergic effects associated with the administration of 200 mg/kg FA or dexamethasone (Dex) 2.5 mg/kg by oral administration. The results of our testing confirm that FA ameliorated nasal symptoms and alleviated nasal epithelium swelling, reduced the goblet cell hyperplasia and eosinophil cell infiltration in the nasal epithelium, and inhibited lung tissue inflammation and Dex as well. Significantly decreased Th2 cytokine (interleukin (IL)-1β, IL-4, and IL-5) expression, and a correspondingly significant increase in Th1 cytokine (IL-12, interferon (IFN)-γ) production, was observed in nasal lavage fluid (NALF) taken from mice that received FA or Dex treatment. FA also reduced the presence of OVA-specific immunoglobulin (Ig) E, OVA-specific IgG1, and histamine levels in serum, and inhibited mast cell degranulation in vitro. In addition, these effects were involved with the reduction in NF-κB phosphorylation. These results suggest that FA restores Th1/Th2 balance and inhibits NF-κB phosphorylation and mast cell degranulation, thereby achieving a notable anti-inflammatory effect. Accordingly, it has the potential to be used as an efficacious therapeutic treatment for AR.

Topics: Amomum; Animals; Cytokines; Disease Models, Animal; Down-Regulation; Immunoglobulin E; Inflammation; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; Phosphorylation; Plant Extracts; Rhinitis, Allergic; Th2 Cells

Allergic rhinitis (AR) is a disease in the nasal mucosa related with Th2 lymphocyte inflammatory action. Dendritic cells (DCs) have been proved that they played a significant role in the development and maintenance of AR. However, there is still a lack of specific therapies for DCs in clinical practice. Shikonin (SHI) is a natural naphthoquinone compound isolated from the Chinese herb Radix Arnebiae. It is reported that SHI can interference the phenotype and function of dendritic cells, so we speculate that SHI may be an effective drug for the treatment of AR. However, the clinical usage of SHI has been limited by the bioactive properties of poor solubility, short retention time and low bioavailability. Therefore, in order to better exert the anti-inflammatory effect of SHI, an efficient SHI delivery system is urgently needed.. We prepared and characterized SHI-PM and NGR-SHI-PM with the thin-film hydration method. We used retrodialysis method to explore the release behavior. We took immunofluorescence to investigate the expression of CD13 in vitro. Then we tested BM-DCs mature cell detection by flow cytometry. An allergic rhinosinusitis murine model, hematoxylin and eosin stain and flow cytometry were established to test the efficiency of anti-inflammation in vivo. At last, western blot analysis and plasmid construction and transfection assay were taken to reveal the molecular mechanisms.. In the present study, we revealed that NGR-modifified could strengthen the intracellular uptake of PM (p < 0.001) and CD13 was high expressed on mature BM-DCs (p < 0.001). NGR-modified could enhance the inhibition of SHI in vitro (p < 0.05). NGR-modifified could increase the distribution of PM in vivo by DiI fluorescently (p < 0.01). NGR-modified could enhance SHI anti-allergic activity in OVA-sensitized mice and enhance the inhibition of SHI on DC maturation in lymph node (p < 0.001). Our findings also suggest that SHI may have the inhibitory effect on AR through NF-κB pathway by targeting PARP.. In summary, we have shown that NGR-PM-SHI could be a novel strategy for targeted treating allergic rhinitis through the NF-κB pathway by targeting PARP.

Topics: Animals; Dendritic Cells; Disease Models, Animal; Mice; Mice, Inbred BALB C; Micelles; Naphthoquinones; Nasal Mucosa; NF-kappa B; Ovalbumin; Poly(ADP-ribose) Polymerase Inhibitors; Polyesters; Polyethylene Glycols; Rhinitis, Allergic

Allergic rhinitis is caused by a breakdown of the Th1/Th2 balance, in which the allergen-induced Th2 immune response predominates over the Th1 immune response, culminating in IgE-mediated anaphylaxis. In this study, we used small extracellular vesicles (sEVs), cell-derived membrane vesicles with a particle size of 100 nm, as simultaneous delivery carriers for allergens (ovalbumin, OVA) and CpG DNA, an adjuvant that can induce a Th1 immune response, for the treatment of allergic rhinitis. sEVs loaded with CpG DNA and OVA(CpG-OVA-sEVs) were successfully prepared. CpG-OVA-sEVs possessed an average particle size of 90 nm and average zeta potential of -30 mV. CpG DNA modification did not influence the uptake of sEVs by dendritic cells and CpG-OVA-sEV can activate dendritic cells. The CpG-OVA-sEVs were delivered to the nasopharynx-associated lymphoid tissue (NALT) of mice and were primarily taken up by the CD11c positive cells after intranasal administration. Intranasally administering CpG-OVA-sEVs significantly enhanced OVA-specific IgG antibody titers in mice models of allergic rhinitis, suggesting a transformed Th1/2 balance. Moreover, The CpG-OVA-sEV administration alleviated allergic symptoms compared to the control group. Further, the amount of IgE secreted in mouse serum decreased. Thus, CpG-OVA-sEVs could be a useful therapeutic method for treating allergic rhinitis.

Topics: Allergens; Animals; Cytokines; Disease Models, Animal; DNA; Extracellular Vesicles; Immunoglobulin E; Immunotherapy; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Th2 Cells

Allergic rhinitis is a systemic disease with high prevalence, which some of its neuropsychological problems have been reported. The primary pathophysiology and mechanism of the neuropsychological dysfunction of AR patients have not been described yet, so here we subjected an animal model of AR to identify any behavioral or seizure threshold changes and to assess the pathophysiology of the disease.. Eighty male BALB/C mice were randomly divided into the allergic rhinitis group and controls. Allergic rhinitis was induced in the first group by administering OVA and aluminum hydroxide intraperitoneally and then nasal injection of OVA for 14 consecutive days. Both groups were subjected to different tests for assessing depressive-like behavior, anxiety, spatial and contextual memory, and learning and seizure threshold. Hippocampus and plasma samples of mice were subjected for analyzing cytokines and immune modulators and for pathology and immunohistochemistry evaluation.. The depressive and anxiety-like behavior were increased in AR, and the spatial learning and memory were disturbed in the AR group. Also, AR mice had lower seizure thresholds compared to controls. Lab data suggested that TLR4, NF-κB, IL-1β, and TNFα expressions were increased in the AR hippocampus as well as their plasma proinflammatory cytokines. Likewise, demyelination, cell death, and M1 macrophage aggregation were increased in the AR hippocampus.. Behavioral and cognitive problems should be taken seriously in patients with AR or other atopic diseases, and more investigating is required to clear the pathophysiology behind it and its treatment.

Topics: Animals; Cytokines; Disease Models, Animal; Hippocampus; Humans; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Neuroinflammatory Diseases; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Seizures; Signal Transduction; Toll-Like Receptor 4

Allergic rhinitis (AR), one of the most common inflammatory diseases, is caused by immunoglobulin E (IgE)-mediated reactions against inhaled allergens. AR involves mucosal inflammation driven by type 2 helper T (Th2) cells. Previously, it was shown that the

Topics: Animals; Cytokines; Disease Models, Animal; Immunization; Inflammasomes; Mice; Mice, Inbred BALB C; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Rhinitis, Allergic; Th2 Cells

Due to the lack of an assessment approach, the image of

Topics: Allergens; Animals; Cytokines; Disease Models, Animal; Histamine; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rats; Rhinitis, Allergic

Topics: Animals; Disease Models, Animal; Dopamine; Mice; Mice, Inbred BALB C; Nasal Mucosa; Olfactory Bulb; Ovalbumin; Rhinitis, Allergic

To investigate the protective effect of. Twenty-four BALB/c mice at ages of 8 to 10 weeks, each weighing approximately 20 g, were randomly divided into four groups, including groups A (blank control group), B (blank intervention group), C (AR model group) and D (AR+HCFP intervention group), with 6 mice in each group. On days 0, 2, 4, 6, 8, 10 and 12, mice in groups A, B, C and D were injected with 200 μL sterile phosphate buffered saline (PBS), 200 μL sterile PBS containing 20 μg HCFP, 200 μL sterile PBS containing 50 μg OVA and 5 mg Al(OH). The mean behavioral score was significantly greater in Group C (6.83 ± 0.50) than in groups A (1.17 ± 0.52) and B (1.33 ± 0.52) (

Topics: Animals; Cytokines; Disease Models, Animal; Echinococcosis; Echinococcus; Echinococcus granulosus; Interleukin-10; Interleukin-4; Interleukin-5; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Transforming Growth Factor beta

Allergic rhinitis (AR) is regarded as a prevalent and non-infectious inflammation in nasal mucosa, and astragalus polysaccharide (APS) could mitigate inflammation.. Herein, this study probed the specific mechanism of APS in inflammatory responses in AR.. APS reduced Treg/Th17 imbalance via suppressing NF-kB expression, thereby ameliorating inflammatory responses in AR.

Topics: Animals; Disease Models, Animal; Forkhead Transcription Factors; Guinea Pigs; Immunoglobulin E; Inflammation; Interleukin-6; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-kappa B; Ovalbumin; Polysaccharides; Rhinitis, Allergic; Sneezing; T-Lymphocytes, Regulatory; Th17 Cells; Transforming Growth Factor beta

To observe the effect of moxibustion, catgut embedding and acupuncture on allergic symptoms and expression of interferon-γ (IFN-γ) and interleukin-4 (IL-4) of nasal mucosa in rats with allergic rhinitis (AR) based on acupoint injection, so as to explore their synergistic effect and related mechanism in relieving AR.. SD rats (half male half female) were randomly divided into normal control, model, acupoint injection (AI), AI+moxibustion, AI+catgut embedding and AI+acupuncture groups, with 8 rats in each group. The AR model was established by intraperitoneal injection of ovalbumin suspension (once every other day for 7 times), and intranasal drop of 0.5% ovalbumin solution (once daily for 7 days). After successful modeling, rats of the AI group received injection of a mixture solution of equal proportion of 1% lidocaine, dexamethasone and transfer factor into "Yingxiang" (LI20) and "Yintang" (EX-HN3) once every 4 days, 4 times altogether. Mild moxibustion or catgut embedment or manual acupuncture was applied to bilateral "Feishu" (BL13) and "Zusanli" (ST36). Both moxibustion (20 min every time) and acupuncture (with the needles retained for 30 min every time) were conducted once daily for 14 times, and catgut embedding was conducted once a week, twice altogether based on acupoint injection. The rats' nasal allergic reaction score (symptom score, 1-3 points) was given according to the times of nose scratching and sneezing, and the running nose state in 30 min, and histopathological changes of nasal mucosa were observed by H.E. staining. The expression levels of IFN-γ and IL-4 in the nasal mucosa were detected by immunohistochemistry and Western blot, separately.. Compared with the normal group, the symptom score and the expression of IL-4 positive cells and protein in nasal mucosa were significantly increased (. Moxibustion or catgut embedment or acupuncture and AI have a synergistic effect in relieving symptoms of AR rats, which may be related to their function in regulating the expression levels of nasal IFN-γ and IL-4 proteins. The therapeutic effect of moxibustion is obviously superior to those of both acupuncture and catgut embedment.

Topics: Acupuncture Points; Acupuncture Therapy; Animals; Catgut; Cytokines; Female; Interleukin-4; Male; Moxibustion; Nasal Mucosa; Ovalbumin; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic

We investigated whether Panax notoginseng saponin (PNS-R1) attenuates allergic rhinitis (AR) through AMPK/Drp1-mediated mitochondrial fission. AR model was established in mice by Ovalbumin (OVA). In vitro, human nasal epithelial cells (HNEpCs) were stimulated using recombinant human interleukin 13 (IL-13). PNS-R1 was administrated in vivo and in vitro. Then, HE staining of nasal tissue, ELISA detection of immunoglobulin E (IgE) and proinflammatory cytokine levels in serum and nasal lavage fluid, flow cytometry analysis of Th1/Th2 ratio and apoptosis, TUNEL staining, Western blot, detection of reactive oxygen species (ROS) and mitochondrial ROS, immunofluorescence analysis of Tom20 and mitochondrial fission protein Drp1 co-localization, and mitochondrial membrane potential detection, were performed. PNS-R1 attenuated allergic symptoms in AR mice, decreased OVA-specific IgE, IL-4, IL-6, IL-8, IL-13, and TNF-α levels, and restored the Th1/Th2 imbalance. Meanwhile, we found that PNS-R1 treatment significantly reduced apoptosis, ROS production, and co-localization of Tom20 and Drp1 in the nasal epithelium of AR mice. In vitro, we found that PNS-R1 upregulated mitochondrial membrane potential and reduced ROS and mitochondrial ROS production as well as Cleaved-caspase-3/9, Bax, Cyt-c, Apaf-1 expression and mitochondrial fission. Mechanistically, we found that PNS-R1 downregulated Drp1 phosphorylation (Ser 616) and Drp1 translocation in an AMPK-dependent manner, promoted MFN2 expression, and reduced TXNIP, NLRP3, Caspase-1, and IL-1β expression. PNS-R1 may protect mitochondrial integrity by inhibiting AMPK/Drp1 and TXNIP/NLRP3 signaling pathway, thereby alleviating AR symptoms in mice. PNS-R1 may have great potential as a therapeutic agent for AR.

Topics: AMP-Activated Protein Kinases; Animals; Disease Models, Animal; Humans; Immunoglobulin E; Interleukin-13; Mice; Mitochondrial Dynamics; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Panax notoginseng; Reactive Oxygen Species; Rhinitis, Allergic; Saponins

Th17 cells are implicated in allergic inflammatory diseases, including allergic rhinitis (AR), though the effect of steroids on Th17 cell-dependent nasal responses is unclear. Herein, we investigated a nasal inflammation model elicited by allergen provocation in mice infused with Th17 cells and its responsiveness against steroid treatment. We transferred BALB/c mice with Th17 cells, which were differentiated in vitro and showed a specific reaction to ovalbumin (OVA). We challenged the transferred mice by intranasal injection of OVA and to some of them, administered dexamethasone (Dex) subcutaneously in advance. Then, we assessed immediate nasal response (INR), nasal hyperresponsiveness (NHR), and inflammatory cell infiltration into the nasal mucosa. The significant nasal inflammatory responses with massive neutrophil accumulation, INR, and NHR were induced upon allergen challenge. Allergen-induced INR and NHR were significantly suppressed by Dex treatment. This study suggested the effectiveness of steroids on Th17 cell-mediated nasal responses in AR.

Topics: Allergens; Animals; Mice; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Th17 Cells

Allergic rhinitis (AR) is one of most prevalent disease and it is urgent need to develop new drug. Tuomin-Zhiti-Decoction (TZD) is a traditional medicinal compound consisting of eleven different herbs and has a significant effect on AR, yet its underlying mechanism is still unknown.. The aim of this study was to confirm the anti-AR effects and the underlying mechanism of TZD. Integrative analysis of network pharmacology and proteomics to explore the common mechanism of TZD treating AR.. Mice were subjected to serial intranasal challenge with ovalbumin (OVA), we examinaed the nasal symptoms, histopathology and Th1/Th2-related cytokines after TZD treatments. Active compounds, potential targets and underlying mechanisms of TZD against AR were systematically clarified by integrating network pharmacology and proteomics analysis. Then we validated the binding affinity between the key potential targets and matching active compounds using molecular docking evaluation.. TZD controlled allergy by reduction of OVA-specific immunoglobulin E (IgE) and histamine release. In nasal tissue, TZD decreased nasal rubbing, sneezing and reduced AR-induced damage to nasal mucosa, accordingly, the nasal symptoms were also clearly ameliorated. Moreover, TZD modulated the balance of Th1/Th2/Th17. The proteomics analysis recognized 41 differentially expressed proteins (DEPs). Integrative analysis of network pharmacology and proteomics, we found IL-6 and CD40 could be potential protein targets of TZD against AR, quercetin and wogonin may play more effective roles in AR. Active core compounds of TZD could bind closely to the key targets by molecular docking.. TZD may have therapeutic potential for treating AR, integrating analysis of network pharmacology and proteomics uncovered the underlying mechanism and targets of TZD, which provides a scientific method for the sensible development of traditional Chinese medicine.

Topics: Animals; Cytokines; Disease Models, Animal; Immunoglobulin E; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Network Pharmacology; Ovalbumin; Proteomics; Rhinitis, Allergic

Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis. Hence, regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis. However, the underlying mechanism is unclear. Dendrobium nobile (Shihu) exhibits anti-inflammatory and immune activities. Hence, in this study, we investigated the mechanism via which Shihu may improve allergic rhinitis. Mouse models of allergic rhinitis with intestinal flora dysbiosis (Model-D, antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy) and normal intestinal flora with allergic rhinitis (Model-N, ovalbumin-induced allergy) were established. The effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed. Allergic symptoms, infiltration of hematoxylin and eosin in the lungs and nose, and the release of various factors [interleukin (IL)-2, IL-4, IFN-γ, IL-6, IL-10, and IL-17] in the lungs were evaluated. The results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis. However, treatment with the Shihu extract effectively reversed these symptoms. Besides, the Shihu extract inhibited the PI3K/AKT/mTOR pathway and increased the level of Forkhead box protein in the lungs. Additionally, the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved regulator T cell differentiation. Furthermore, in the Model-D group, the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora. Screening was performed to determine which intestinal flora was positively correlated with Treg differentiation using Spearman's correlation analysis. In conclusion, we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using Traditional Chinese Medicine to improve allergic rhinitis.

Topics: Animals; Cytokines; Dendrobium; Disease Models, Animal; Drugs, Chinese Herbal; Dysbiosis; Gastrointestinal Microbiome; Inflammation; Mice; Mice, Inbred BALB C; Ovalbumin; Phosphatidylinositol 3-Kinases; Pneumonia; Rhinitis, Allergic

To identify the effect of long noncoding RNA (lncRNA) FR215775 in regulating CD4+ T cells on murine models of allergic rhinitis (AR), the expression of lncRNA FR215775 in primary Th2 cells was detected through qRT-PCR. After knocking down the expression of lncRNA FR215775 via Sh-FR215775-Ads, Cell Counting Kit-8, cytometric bead array, and fluorescence-activated cell sorting were performed to determine its functions in vitro. Moreover, lncRNA FR215775-silencing or nonsilencing cells were injected intravenously into AR mice. Then, hematoxylin and eosin, Alcian blue-periodic acid Schiff, and toluidine blue staining were performed, and the levels of IL-2, IL-4, IL-5, IL-6, IL-10, IL-17A, IFN-

Topics: Animals; Cytokines; Disease Models, Animal; Inflammation; Interleukin-4; Interleukin-5; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; RNA, Long Noncoding; Th2 Cells

Allergic rhinitis (AR) is a common immune disease of the nasal mucosa characterized with immunoglobulin E (IgE)-mediated allergic inflammation after exposure to allergens in susceptible population. Previous reports have demonstrated that the bone marrow mesenchymal stem cells (BMSCs) could reduce allergic inflammation. However, there is little knowledge about whether the culture supernatant of BMSCs (conditioned medium, CM) has similar anti- inflammatory potential in treating AR.. The study aimed to evaluate the immunoregulatory effects of conditioned medium derived from BMSCs (BMSC-CM) on allergic inflammation in an AR mouse model.. The AR murine model was induced by repeated sensitization and challenges with ovalbumin (OVA). Subsequently the allergic symptoms of AR mice, cytokine levels, the histopathological features of the nasal mucosa and T helper 1 (Th1) : T helper 2 (Th2) cells ratio were evaluated.. Treatment with BMSC-CM was found as effective as BMSCs in reducing allergic symptoms and inhibiting eosinophilic infiltration in the nasal mucosa. After BMSC-CM or BMSCs administration, the OVA-specific IgE and interleukin 4 levels in serum decreased and interferon gamma level increased compared with AR mice treated with uncultured fresh medium. Flow cytometry analysis revealed a decrease in Th1:Th2 cells ratio after OVA-sensitization and the ratio was reversed by BMSC-CM and BMSCs treatments. Furthermore, the data revealed that BMSC-CM suppressed the production of signal transduction and activator of transcription 6 (. BMSC-CM could ameliorate allergic inflammation and regulate the balance of Th cells, and the underlying mechanism was closely related to

Topics: Animals; Anti-Inflammatory Agents; Culture Media, Conditioned; Disease Models, Animal; Immunity; Immunoglobulin E; Inflammation; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Signal Transduction

Allergic rhinitis (AR) is a heterogeneous disease and its pathogenesis is still unclear. Growing clinical evidence has thrown light on the key role of NOD-like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation of allergic disease. However, the effect of NLRP3 activation in macrophages for AR has not been elucidated. This study aims to investigate the role of NLRP3 in ovalbumin (OVA)-stimulated bone marrow-derived macrophages (BMDMs) and to confirm the impact of macrophage pyroptosis in allergic rhinitis.. Nasal inflammation levels were assessed by H&E and dual immunofluorescence staining. BMDMs were cultured and were stimulated with OVA in the presence or absence of MCC950 to further investigate the effect of NLRP3 activation in macrophages. The cell lysates and supernatants were harvested to measure NLRP3 and downstream molecules, as well as cell rupture, and IL-1β production. Besides, an OVA-exposed AR mouse model was developed, and the histopathology in nasal mucosa, and the relationship between macrophage pyroptosis and local inflammation were detected. The inhibitory role of MCC950 was also evaluated.. The present results uncovered that the number of macrophages and NLRP3 expression were increased in the nasal mucosa of AR subjects, and upregulation of macrophage pyroptosis contributed to local allergic inflammation. In addition, the OVA challenge induced NLRP3 inflammasome activation in BMDMs, as evidenced by enhanced expressions of NLRP3-ASC-caspase-1 inflammasome, gasdermin D, production of IL-1β, and increased macrophage lysis. Furthermore, inhibition of NLRP3 inflammasome attenuated nasal inflammation, accompanied by a reduced number of inflammatory cells and lower levels of IL-1β and OVA-specific IgE.. Our results indicate that NLRP3 inflammasome played an important role in allergic airway inflammation by activating macrophage's pyroptotic cell death and releasing inflammatory mediators to local tissues. Inhibition of NLRP3 inflammasome-mediated pyroptosis could be a promising therapeutic strategy for ameliorating inflammatory responses in allergic rhinitis.

Topics: Animals; Humans; Inflammasomes; Inflammation; Interleukin-1beta; Macrophages; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Pyroptosis; Rhinitis, Allergic

Allergic rhinitis (AR) is an immunoglobulin E-mediated type 2 inflammation of the nasal mucosa that is mainly driven by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s). CD226 is a costimulatory molecule associated with inflammatory response and is mainly expressed on T cells, natural killer cells, and monocytes. This study is aimed at elucidating the role of CD226 in allergic inflammatory responses in murine AR using global and CD4

Topics: Animals; Cytokines; Disease Models, Animal; Immunity, Innate; Lymphocytes; Mice; Mice, Inbred BALB C; Mice, Knockout; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Th2 Cells

Increased expression of substance P (SP) and neurokinin-1 receptor (NK1R) has been noticed in patients with allergic rhinitis (AR) and allergic asthma (AA). However, little is known of the expression of SP and NK1R in monocytes and B cells of AR and AA. In the present study, the expression levels of SP and NK1R were determined by flow cytometry and mouse AR and AA models. The results showed that both percentages of SP+ monocytes and SP+ B cells, and mean fluorescence intensity (MFI) of SP in monocytes were elevated in the blood of AA and AR combined with AA (ARA) patients. Similarly, the percentages of NK1R+ monocytes were elevated in the blood of AR, AA, and ARA patients. Allergens Artemisia sieversiana wild allergen extract (ASWE), house dust mite extract (HDME), and Platanus pollen allergen extract (PPE) increased the expression density of SP molecules (determined by MFI) in an individual monocyte of AR patients. HDME and PPE appeared to enhance SP and NK1R expression in the B cells of ARA and AR patients. In the mouse AR and AA models, the percentages of NK1R+ monocytes and B cells were elevated in blood following OVA (ovalbumin) sensitization and challenge. Knocking out the FcεRI molecule completely abolished the OVA-induced upregulation of expression of NK1R in monocytes and B cells of AA mice. In conclusion, upregulated expressions of SP and NK1R may contribute to the pathogenesis of airway allergy.

Topics: Allergens; Animals; Asthma; Mice; Monocytes; Ovalbumin; Receptors, Neurokinin-1; Rhinitis, Allergic; Substance P

Nonylphenol (NP) can be widely used as a plasticizer, surfactant, antioxidant, textile printing, dyeing additive, and pesticide emulsifier. Animal studies have shown that NP aggravates ovalbumin (OVA)-induced allergic rhinitis (AR); however, the exact mechanism underlying its action has not yet been detailed. This study aimed to explore the aggravation of the AR inflammatory response following NP exposure and its possible mechanism. The AR mouse model was constructed using OVA. Under NP exposure, allergic nasal symptoms were observed, eosinophil infiltration was assessed by Sirius red staining, and the levels of IL-4, IL-5, and IL-13 in nasal mucosa samples were detected using cytometric bead array. The mRNA levels of OX40/OX40L and GATA3 in nasal mucosa were detected by qPCR, and the expression levels of the TSLP and JAK1/2-STAT3 signaling pathway components were also identified. Our results suggest that NP exposure exacerbated allergic nasal symptoms and that eosinophils accumulated in nasal mucosa after OVA challenge. The levels of the typical T helper 2 cytokines, as well as the mRNA levels of OX40/OX40L and GATA3, were elevated in the nasal mucosa of OVA-challenged mice exposed to NP. In addition, NP exposure elevated the TSLP, TSLPR, IL-7R, p-JAK1, p-JAK2, and p-STAT3 levels in the nasal mucosa after OVA stimulation. Overall, the present study suggests NP can exacerbate OVA-induced AR inflammatory responses; furthermore, this aggravating effect of NP may be related to the TSLP-TSLPR/IL-7R and JAK1/2-STAT3 signaling pathways.

Topics: Animals; Cytokines; Disease Models, Animal; Immunoglobulins; Janus Kinase 1; Mice; Mice, Inbred BALB C; Ovalbumin; Phenols; Receptors, Cytokine; Receptors, Interleukin-7; Rhinitis, Allergic; RNA, Messenger; Signal Transduction; STAT Transcription Factors; Th2 Cells; Thymic Stromal Lymphopoietin

Allergic rhinitis is one of the common chronic inflammatory diseases of the nasal mucosa. In order to investigate the effect of zinc on ovalbumin induced allergic rhinitis in BALB/C male mice based on NF-KB signaling pathway, thirty BALB/C male mice are randomly divided into three groups: control group, ovalbumin induced allergic rhinitis asthma group and zinc intervention group. The experimental results show that Zinc supplementation in allergic asthma mice with allergic rhinitis correct the immune response of TH2 cells by inhibiting THE NF-KB signaling pathway, reduce the infiltration of inflammatory cells into lung nasal tissue, and reduce airway co-hyperreactivity to improve the clinical symptoms of asthma and play an immune protective role.

Topics: Animals; Asthma; Cytokines; Disease Models, Animal; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Signal Transduction; Zinc

Shufeng Jiedu capsule (SFJDC) has been widely used as a conventional Chinese pharmaceutical agent for various upper respiratory infections, including acute lung injury, acute respiratory distress syndrome and allergic rhinitis (AR). However, its mechanism in AR remains unclear.. The present study aimed to decipher the antiallergic inflammatory effect of SFJDC in an AR model with olfactory dysfunction. Specifically, we wanted to explore whether SFJDC can improve the olfactory abnormality in AR mice and reduce the levels of inflammatory factors in the olfactory epithelium (OE) and olfactory bulb (OB).. To address the above issues, we constructed an AR model using C57BL/6 mice, which were sensitised and challenged with ovalbumin (OVA) by intraperitoneal injection. SFJDC (0.045 or 0.18 g/kg) was delivered by gavage administration 1 h prior to the intraperitoneal injection of OVA. The control mice received saline alone. Then, the animals were assessed according to the presence of nasal symptoms and nasal inflammation, and a buried food test was used to evaluate olfactory function. The levels of proteins involved in the AMPK/mTOR autophagy pathway in the OE and OB were investigated by western blotting and fluorescence staining.. After OVA induction of AR and drug administration, we found that SFJDC significantly ameliorated the nasal symptoms and allergic inflammatory reaction of the nasal mucosa superior to cetirizine. A behavioural test indicated that the mice with AR had olfactory dysfunction, and SFJDC can ameliorate this behavior deficiency. Meanwhile, SFJDC clearly reduced the neuroinflammation level in OE tissue. In addition, SFJDC increased p-mTOR and decreased p-AMPK, beclin1, LC3 and cleaved caspase-3 levels in the OE.. In addition to antibacterial and antiviral activities, SFJDC has marked anti-inflammatory effects in AR mice. Its mechanism of action in the nasal cavity involves inhibition of upregulated anti-inflammatory cytokines, modulation of autophagy and apoptosis levels and regulation of autophagy through the AMPK/mTOR pathway in the OE tissue of AR mice. Hence, SFJDC is a promising drug for AR, and clinical trials should further validate the therapeutic impact of SFJDC on AR with olfactory dysfunction.

Topics: AMP-Activated Protein Kinases; Animals; Anti-Allergic Agents; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiviral Agents; Autophagy; Beclin-1; Caspase 3; Cetirizine; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Olfaction Disorders; Ovalbumin; Rhinitis, Allergic; TOR Serine-Threonine Kinases

In East Asia, the dried root of

Topics: Animals; Anthraquinones; Anti-Allergic Agents; Antipyretics; beta-N-Acetylhexosaminidases; Cytokines; Disease Models, Animal; Ethanol; Immunoglobulin E; Interleukin-13; Interleukin-3; Interleukin-4; Lithospermum; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Rhinitis, Allergic

α-Linolenic acid (ALA) is a natural essential fatty acid widely found in plant seed oils and beans, which shows positive anti-inflammatory and antiallergic effects. In our previous study, ALA was proven to bind tightly to the seven protein targets closely associated with allergic rhinitis (AR) by molecular docking, which indicates that ALA may have a potential role in the treatment of AR. A mouse model of AR induced by ovalbumin (OVA) was adopted in this study to explore the therapeutical effect and potential mechanism of ALA in treating AR. Results demonstrated that ALA remarkably relieved the nasal symptoms, reduced the OVA-sIgE level in the serum, relieved the histopathological injuries, and downregulated the mRNA expression levels of IL-6 and IL-1β in the nasal mucosa. ALA also remarkably moderated the imbalance of Th1/Th2 cells, increased the mRNA expression levels of T-bet and STAT1, and reduced GATA3 and STAT6. ALA was proven to have a substantial therapeutic effect on mice with AR, and the underlying mechanism was likely to be the regulation of Th1/Th2 imbalance through the JAK/T-bet/STAT1 and JAK/GATA3/STAT6 pathways. This study provides a specific experimental basis for the clinical use and drug development of ALA in the treatment of AR.

Topics: alpha-Linolenic Acid; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Inflammation; Interleukin-6; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Nasal Mucosa; Ovalbumin; Plant Oils; Rhinitis, Allergic; RNA, Messenger; Th2 Cells

Ubiquitin‑specific peptidase 25 (USP25) is a key deubiquitylase belonging to the USP superfamily that is primarily involved in inflammation and the immune response. Thymic stromal lymphopoietin (TSLP) is an epithelial‑derived cytokine that is regarded as the master switch that initiates and maintains the type 2 immune response in allergic rhinitis (AR). However, the molecular mechanisms by which USP25 regulates TSLP signaling in the nasal epithelium in AR remain unclear. The present study assessed the protein expression levels of USP25 in the nasal epithelium of patients with AR. Moreover, USP25 knockout (KO) and wild‑type (WT) mice were treated with ovalbumin (OVA) to establish a model of AR. The results of western blotting and immunohistochemistry in the present study demonstrated that the protein expression levels of USP25 were significantly decreased in the nasal mucosa of patients with AR and AR mice, whereas the protein expression levels of TSLP were significantly increased. Allergic inflammation was more severe in USP25 KO mice compared with WT mice exposed to OVA, as demonstrated by increased nose scratching and sneezing, increased eosinophil infiltration, goblet cell hyperplasia and enhanced T helper type 2 (Th2) cytokine production. The results of

Topics: Animals; Cytokines; Deubiquitinating Enzymes; Disease Models, Animal; Down-Regulation; Humans; Inflammation; Mice; Mice, Inbred BALB C; Mice, Knockout; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Thymic Stromal Lymphopoietin; TNF Receptor-Associated Factor 3; Ubiquitin Thiolesterase; Ubiquitin-Specific Proteases

In this study, the immunomodulatory effects and mechanism of action of a novel water-extracted Lonicera japonica polysaccharide (WLJP) on allergic rhinitis (AR) was investigated. For the efficacy of WLJP, behavioral symptoms (rubbing and sneezing), serum inflammatory factors, pathological damage, splenic T cell differentiation, gut microbiota imbalance, and protein analysis of the nasal mucosa and colon were assessed. WLJP and the NLRP3 inhibitor, CY-09, were co-evaluated in the AR model established using LPS + IFN-γ-induced THP-1 cells. The WLJP group showed decreased serum inflammatory factors, eosinophils, goblet cells, NLRP3 inflammasomes, splenic Th17 cell differentiation, and expression of IL-17, p-p65, and gut NLRP3 in the nasal mucosa while maintaining gut microbiota balance, repairing the mechanical barrier, and significantly improving AR behavioral symptoms. In vitro interaction analysis showed a significant interaction between CY-09 and WLJP. In conclusion, WLJP improves AR by repairing the gut barrier and inhibiting NLRP3 inflammasome-driven inflammation and the Th17 immune response.

Topics: Animals; Disease Models, Animal; Inflammasomes; Inflammation; Interleukin-17; Lipopolysaccharides; Lonicera; Mice; Mice, Inbred BALB C; Nasal Mucosa; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Rhinitis, Allergic; Water

Allergic rhinitis (AR) is a series of reactions to allergen mediated by immunoglobulin E (IgE) and is one of the most common allergic diseases that affects children. Traditional Chinese Medicine, due to its diverse regulatory functions, may offer new strategies for AR therapy. Huanggui Tongqiao Granules (HTG) is a Chinese formula consisting of twelve herbs and has long been prescribed for patients with AR. The aim of this study is to determine the possible targets and action mechanisms of HTG for the AR treatment. SymMap database and TMNP algorithm were employed to show that interferon-gamma (IFN-gamma), acting as a molecular link between immunity and neural circuits, is the involved key target. The enrichment of immune and virus-related signaling pathways indicated the neuroimmunomodulatory potential of HTG. Then, AR mouse model was established by ovalbumin (OVA) challenge and was used to verify the therapeutic effects of HTG in vivo. HTG significantly relieved AR symptoms and nasal mucosal inflammation, reduced OVA-specific IgE levels and balanced IFN-gamma/IL-4 ratio. Moreover, transcriptional profile based on clinical data presented that blood cell-specific IFN-gamma co-expressed gene module (BIM) was underexpressed in AR patients, further validating the potential of IFN-gamma as target for AR. Collectively, these findings suggest that HTG could be a promising candidate drug for AR.

Topics: Algorithms; Animals; Cytokines; Disease Models, Animal; Immunoglobulin E; Interferon-gamma; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic

Allergic disorders are common all over the world. The pathogenesis of allergy is unclear. Therapies for allergic disorders require improvement. Endoplasmic reticulum (ER) stress is one of the factors influencing immune response. The purpose of this study is to improve the effectiveness of immunotherapy for experimental respiratory allergy by targeting the ER stress signal pathway.. Committed CD4. ER stress was detected in antigen-specific CD4. ER stress can be detected in CD4

Topics: Animals; Immunotherapy; Mice; Ovalbumin; Receptors, Antigen, T-Cell; Rhinitis, Allergic; T-Lymphocytes, Regulatory; Ubiquitin-Protein Ligases

Topics: Animals; Artemisia; Asthma; Cell Degranulation; Cytokines; Disease Models, Animal; Immunoglobulin G; Inflammation; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Rhinitis, Allergic; Th1 Cells; Th2 Cells; Transcription Factors

Topics: Allergens; Animals; Cytokines; Disease Models, Animal; Immune Tolerance; Immunoglobulin E; Immunoglobulin G; Interleukin-10; Interleukin-4; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Transforming Growth Factor beta

Allergic rhinitis (AR) is an allergic disease induced by the T helper 2 (TH2) lymphocyte immune response, where its mediators are the primary cause of clinical symptoms. Environmental factors are the primary determinants of the allergic response in genetically susceptible individuals. This study investigates the effects of climate conditions (warm, cold, humid, and dry) on allergic rhinitis. AR models were created in mice under 4 different conditions. We investigated AR-related behavior (sneezing and nose rubbing), as well as total immunoglobulin E (IgE), histamine, interleukin-4 (IL-4), leukotriene (LT) B4 and LTC4 levels, and gene expression of CysLT1R, HRH1, and MUC5a. Nose rubbing, histamine levels, and the expression of MUC5a and HRH1 were increased in AR models in cold conditions, and sneezing was increased in AR models kept in dry conditions. LTB4 and LTC4 levels and the expression of CysLT1R in AR models kept in a wet environment also significantly increased compared with the control group. The levels of total IgE and IL-4 showed no significant changes. Air temperature and humidity affect AR pathophysiology, and weather conditions can be essential in controlling AR.

Topics: Animals; Disease Models, Animal; Histamine; Humidity; Immunoglobulin E; Interleukin-4; Leukotriene C4; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sneezing; Temperature

Allergic rhinitis (AR) is a common type of inflammatory disease with symptoms including rhinorrhea, fatigue, sneezing, and disturbed sleep. AR affects nearly 40% of peoples worldwide with the increased numbers of new cases. In this work, the study was conducted to disclose the anti-inflammatory and antiallergic properties of cirsilineol against the ovalbumin (OVA)-sensitized AR in mice. AR was provoked in BALB/c mice through the OVA challenge 30 days along with 10 and 20 mg/kg of cirsilineol treatment. The nasal symptoms, i.e., rubbing and sneezing was monitored after the final OVA challenge. The status of OVA-specific IgE, PGD2, and LTC4 was investigated using assay kits. The status of pro-inflammatory markers also examined using assay kits. The levels of oxidative markers, SOD activity, and pro-inflammatory markers in the spleen mononuclear cells (SMEs) were studied by using respective assay kits. The mRNA expression of TXNIP was assessed using RT-PCR study. The 10 and 20 mg/kg of cirsilineol treatment effectively decreased the sneezing and nasal rubbings in OVA-provoked mice. Cirsilineol also decreased the IgE, PGD2, and LTC4 status in the AR animals. The status of pro-inflammatory markers, i.e., IL-4, IL-5, IL-6, IL-33 and TNF-α was found to be decreased in the cirsilineol administered AR mice. Cirsilineol effectively reduced the ROS and MDA and improved SOD in the OVA-challenged SMCs. The mRNA expression of TXNIP was appreciably suppressed by the cirsilineol treatment. Altogether, these findings proved the beneficial actions of cirsilineol against the OVA-triggered AR in mice. The additional studies on the cirsilineol could lead to the development of new drug for AR management.

Topics: Animals; Anti-Allergic Agents; Biomarkers; Carrier Proteins; Cells, Cultured; Disease Models, Animal; Eosinophils; Flavones; Histamine; Immunoglobulin E; Leukotriene C4; Mice, Inbred BALB C; Nasal Lavage Fluid; Ovalbumin; Oxidative Stress; Prostaglandin D2; Rhinitis, Allergic; Spleen; Thioredoxins

Allergic rhinitis (AR) is a well-documented type 2 helper T (Th2) cell-mediated allergic disease that is accompanied by symptoms such as nasal rubbing, sneezing, itching, and rhinorrhea. Angelica gigas (AG) is traditional oriental medicine, and its dried root is widely used for the treatment of anemia, as a sedative, and as a blood tonic.. The effects of AG on allergic diseases including AR are currently unclear; therefore, we aimed to investigate the effects of AG extract (AG-Ex) in ameliorating AR.. The cytotoxicity of AG-Ex was analyzed by EZ-Cytox or MTS assay in splenocytes, differentiated Th2 cells, and human nasal epithelial cells (HNEpC). The changes of Th2 cells activation were determined by the secretion levels of cytokines and chemokines using cytometric bead array in splenocytes and differentiated Th2 cells. The expression levels of eotaxin-3 and periostin were analyzed using an ELISA. AR was induced by ovalbumin in BALB/c mice and the ameliorating effects of AG-Ex were assessed by their clinical symptoms.. The secretion of Th2 cytokines such as IL-4, IL-5, and IL-13 was inhibited by the AG-Ex treatment in the splenocytes and differentiated Th2 cells. The treatment also suppressed allergic responses including the secretion of eotaxin-3 and periostin in human nasal epithelial cells (HNEpC). Moreover, the administration of AG-Ex to the OVA-induced AR mice improved their clinical symptoms, including behavioral tests, immune cell counts, histopathological analysis, and changes in serum parameters.. The results of this study suggest that AG-Ex ameliorates AR by inhibiting Th2 cell activation and could thus be utilized as a treatment for Th2-mediated allergic diseases in the future.

Topics: Angelica; Animals; Cytokines; Disease Models, Animal; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Plant Extracts; Rhinitis, Allergic; Th2 Cells

Allergic rhinitis (AR) is an immune inflammatory-related disorder that affects the nasal mucosa. Free radicals play a crucial role in the expansion of allergic reaction and the researcher used the antioxidant therapy to treat the disease. Trachyspermum ammi L. (Ajwain oil) is popular traditional medicine. It has been proved their potential effect on various diseases. Ajwain oil showed anti-tumor, antioxidant, antidiabetic, anti-inflammatory, and anti-bacterial properties. Yet, the anti-allergic effect of Ajwain oil is still not explored. In this experimental study, an ovalbumin (OVX)-induced AR model was used to scrutinize the anti-allergic, antioxidant and anti-inflammatory effects of Ajwain oil.. OVX was used to establish the AR model (sensitization days 1, 8, and 15) and given the oral treatment of Ajwain oil and Montelukast for 13 days. The spleen, lungs, and body weight were estimated. Sneezing, nasal discharge and rubbing are also estimated. Immunoglobin-E (IgE), histamine, malondialdehyde (MDA), superoxide dismutase (SOD), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and inflammatory cytokines were scrutinized.. Ajwain oil significantly (p < .001) suppressed sneezing, nasal discharge and nasal rubbing along with increasing the spleen, lung and body weight. Ajwain oil significantly (p < .001) decreased the level of IgE, histamine, MDA, Nrf2, HO-1, and increased the level of SOD. Ajwain oil significantly (p < .001) suppressed the number of eosinophils, neutrophils, macrophages, and epithelial cells. Ajwain oil significantly prevented the activation of the NF-κBp65 and STAT3 signaling pathways that led to enhancing the synthesis of anti-inflammatory cytokines and reducing the inflammatory, allergen-specific type 2T helper cells (Th2), Th17 cytokines.. The obtained data suggests that Ajwain oil has a promising anti-allergic against allergic rhinitis in mice via anti-allergic, antioxidant, and anti-inflammatory effects.. Allergic rhinitis is a serious life-threatening disease. Inflammatory reaction plays an important role in the expansion of AR diseases. Ajwain oil considerably increased the spleen weight and reduced lung weight. Ajwain oil suppressed the nasal rubbing, sneezing, and nasal discharge. Ajwain oil considerably suppressed the immunoglobin and inflammatory cytokines. The result suggests that Ajwain oil having the potential effect against the allergic rhinitis.

Topics: Animals; Mice; Mice, Inbred BALB C; Ovalbumin; Oxidative Stress; Rhinitis, Allergic; Th2 Cells

Allergic rhinitis (AR) is one of the most common noninfectious respiratory diseases caused by immunoglobulin E (IgE) response.. The study sought to explore the relationship between lncRNA MIAT and miR-10b-5p and their interaction in the regulation of allergic phenotypes in allergic rhinitis (AR) mice.. A mice model of AR was constructed using ovalbumin (OVA) sensitization. AR mice were treated with miR-10b-5p agomiR and LNA mediated lncRNA MIAT. The targeting relationship between MIAT and miR-10b-5p was analyzed by the ENCORI website and dual-luciferase reporter assay. The numbers of rubbing and sneezing of mice were counted. Hematoxylin-eosin (HE) staining visualized the eosinophils infiltration in nasal mucosa tissues of mice. The percentage of Th17 cells was quantitated by flow cytometry analysis. ELISA was used to detect the levels of serum OVA-specific IgE, the Th12 cytokine IL-4, and inflammatory cytokines (IL-6, IL-17).. MIAT was up-regulated in the nasal mucosa of AR mice, while miR-10b-5p was down-regulated. MIAT directly suppressed miR-10b-5p expression in AR mice. The numbers of rubbing and sneezing, the percentage of Th17 cells, and the levels of OVA-specific IgE, IL-4, IL-6, and IL-17 in AR mice were decreased by miR-10b-5p overexpression, which was reversed by MIAT overexpression. The eosinophils infiltration in AR mice was inhibited by miR-10b-5p overexpression, which was also reversed by MIAT overexpression.. The present study demonstrates that MIAT overexpression Promotes allergic inflammation and symptoms by activating Th17 immune response via miR-10b-5p inhibition.

Topics: Animals; Cytokines; Disease Models, Animal; Inflammation; Mice; Mice, Inbred BALB C; MicroRNAs; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; RNA, Long Noncoding

To explore the regulatory effects of microRNA (miRNA)-224 and its potential target gene, cyclin dependent kinase 9 (CDK9), in the pathological process of allergic rhinitis (AR).. To investigate the role of miR-224 and CDK9, it was screened by bioinformatics prediction software and verified by dual-luciferase reporter assay. The mouse model of AR was established by ovalbumin (OVA).The animal models were intervened with miR-224 agomir, negative control agomir, and saline respectively. The symptoms of sneezing and nasal rubbing were recorded. The expressions of miR224, CDK9, and cytokines in the nasal mucosa of different groups were analyzed by rt-PCR or western blotting. Enzyme-linked immunoassay (ELISA) was used to evaluate the levels of IgE and Histamine (HA) in the serum. The infiltration of inflammatory cells in the nasal mucosa was studied by immunohistochemistry. The expression and distribution of CDK9 in the nasal mucosa of mice were revealed by immunofluorescence.. In the nasal mucosa of the animal models, the level of miR-224 was downregulated, while that of CDK9 was upregulated. The upregulation of miR-224 by miR-224 agomir reduced the frequencies of nasal rubbing and sneezing, the expression of CDK9, the levels of cytokines, and the concentrations of IgE and HA. Moreover, miR-224 appeared to attenuate the infiltration of inflammatory cells and hypersecretion of glands in the nasal mucosa. The expression of CDK9, which was distributed under the mucosa, especially in the submucosa interstitial tissue, was significantly reduced.. MiR-224 affected the pathogenesis of AR by targeting CDK9. It proves that miR-224 could be a novel potential therapeutic target for AR.

Topics: Animals; Cyclin-Dependent Kinase 9; Cytokines; Disease Models, Animal; Histamine; Immunoglobulin E; Inflammation; Mice; Mice, Inbred BALB C; MicroRNAs; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sneezing

Topics: Abietanes; Animals; Cell Degranulation; Cell Line; Disease Models, Animal; Mast Cells; Mice; Ovalbumin; Phospholipase C gamma; Protein Kinase C; Rhinitis, Allergic

Allergic rhinitis (AR) is a complex, chronic immunoinflammatory disorder of the membrane lining of the nasal mucosa. D-Pinitol is considered a cyclic polyol with a potential effect against various allergies. In the present study, we evaluated the anti-allergic effect of pinitol on ovalbumin (OVA)-induced AR model in mice. BALB/c mice were initially sensitized with an intraperitoneal injection of OVA and divided into 5 groups (n=18, in each group) for a treating schedule of distilled water (DW), montelukast (10 mg/kg), and pinitol (5, 10, and 20 mg/kg) through the mouth. Two saline-injected groups were considered as controls by orally administrating DW and pinitol 20. Thereafter, test and control groups were intranasally challenged by OVA and saline, respectively. Our results showed that the OVA challenge caused a marked elevation in AR symptoms like nasal rubbing, sneezing, and discharge which were remarkably diminished using pinitol (10 and 20 mg/kg) and the results were comparable with montelukast. Additionally, increased levels of total and OVA-specific serum Immunoglobulin (Ig) E and IgG1 were significantly attenuated by pinitol as compared to the control group but not the montelukast group. In AR-induced mice, pinitol had significant modulatory effects on representative markers of Th2 (GATA binding protein 3), signal transducer and activator of transcription-6, Interleukins (IL)-4, IL-5, IL-13, suppressors of cytokine signaling 1, Toll-like receptor 4, and myeloid differentiation factor 88), and Type 1 T helper (Th1) immune responses (T-box protein expressed in T cells and Interferon-gamma) as well as the histopathological aberrations induced in the nasal mucosa. In conclusion, Pinitol had potential effects on OVA-induced AR mice through amelioration of nasal symptoms and balancing the Th1/Th2 immune responses during the allergic rhinitis condition.

Topics: Animals; Anti-Allergic Agents; Inositol; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Random Allocation; Rhinitis, Allergic; Th1-Th2 Balance; Treatment Outcome

Chronic inflammation of the nasal mucosal tissues plays an important role in the pathogenesis of allergic rhinitis (AR). Aberrantly-expressed micro ribonucleic acid (miRNA) has been found to have strong associations with the inflammatory reactions in allergic diseases; however, its functional significance and molecular mechanism in AR remains unclear. The purpose of this study is to determine the functional role and mechanism of miR-181a-5p in AR.. Allergic inflammatory reaction was induced by ovalbumin in human nasal epithelial cell line RPMI2650. The anti-inflammatory effects of miR-181a-5p were evaluated by examining pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α)) in the culture of RPMI-2650 cells stimulated by ovalbumin, using quantitative real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Luciferase assay and gain-of-function assay were used to investigate the association of miR-181a-5p and IL-33/p38 MAPK axis.. MiR-181a-5p was significantly downregulated in mucosal tissues of AR patients and in RPMI-2650 cells treated with ovalbumin. The overexpression of miR-181a-5p showed prominent suppression of inflammatory cytokine production in RPMI-2650 cells with the stimulation of ovalbumin. MiR-181a-5p directly targeted, and negatively regulated IL-33 to suppress the activation of p38 MAPK signalling.. The results suggest that miR-181a-5p restricted allergic inflammation through inhibition of IL-33/p38 MAPK pathway, indicating miR-181a-5p may play an anti-inflammatory role in AR.

Topics: Epithelial Cells; Humans; Inflammation; Interleukin-33; MicroRNAs; Ovalbumin; p38 Mitogen-Activated Protein Kinases; Rhinitis, Allergic

According to recent epidemiologic studies, exposure to fine particulate matter (particulate matter 2.5 ≤ µm [PM2.5]) in the air increases the incidence and severity of allergic rhinitis (AR). Ursolic acid (UA) has activities in immune regulation and anti-inflammatory. However, the role of UA intervention on PM2.5-exposed AR remains unknown. In this study, we investigated the effects of UA on tissue remodeling and mucus hypersecretion in a rat model of AR after PM2.5 exposure.. AR was induced in rats with ovalbumin (OVA) and they were exposed to ambient PM2.5(200 µg/m. UA group showed reduced goblet cell hyperplasia and collagen deposition in the nasal mucosa which exacerbated after PM2.5 exposure, as reflected by PAS and MT staining when compared with the ARE group. Immunohistochemical results showed that the expression of MUC5AC in the UA group was lower than that in the ARE group.. Analysis of our data indicated that UA could attenuate nasal remodeling and mucus hypersecretion in aggravation of AR after PM2.5 exposure, which may be the pathophysiologic mechanisms for the prevention of AR exacerbated by exposure to PM2.5.

Topics: Animals; Disease Models, Animal; Mucus; Nasal Mucosa; Ovalbumin; Particulate Matter; Rats; Rhinitis, Allergic; Triterpenes; Ursolic Acid

Allergic rhinitis (AR) is a serious public health concern worldwide. Therefore, the present study was conducted to scrutinize the protective effect of corynoline (COR) against ovalbumin (OVA)-induced AR in BALB/c mice. The effect of COR was investigated on various parameters, such as nose-rub score, histamine intensity, level of cytokines, and NF-κB binding activity. It was found that COR causes a significant reduction in the nose-rub score with a reduction in histamine intensity. It also causes reductions in cytokines, such as TNF-α, IL-1β, and MIP-2, in comparison to OVA-challenged mice. COR reduces the gene expression of active caspase-1 in Western blot analysis, together with inhibition of NF-κB binding activity. The inhibitory effect on NF-κB binding was further substantiated by docking analysis, where COR excellently docked into the active site of NF-κB via the creation of H-bond and π-cation interactions with Lys145. Taken altogether, our results demonstrated that COR could be used as a potential therapeutic agent against AR.

Topics: Animals; Berberine Alkaloids; Caspase 1; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Mice; Mice, Inbred BALB C; Molecular Structure; NF-kappa B; Ovalbumin; Protective Agents; Rhinitis, Allergic; Structure-Activity Relationship

The present study aimed to investigate whether microRNA (miR)‑31 exerted therapeutic potential in allergic rhinitis (AR) and to explore its underlying mechanism. Firstly, the expression levels of miR‑31 were detected by reverse transcription‑quantitative PCR in the nasal mucosa of patients and mice. Subsequently, an ovalbumin (OVA)‑induced animal model of AR was constructed. Allergic symptom score, histopathological characteristics, OVA‑specific immunoglobulin E (IgE) titers, and T‑helper (Th)1 and Th2 cell‑related cytokine levels were analyzed in OVA‑sensitized mice, miR‑31‑overexpressing mice, miR‑negative control mice and control mice. Furthermore, interleukin (IL)‑13‑stimulated nasal epithelial cells (NECs) were used to assess the effects of miR‑31 on the production of IL‑13‑induced inflammatory cytokines and mucin 5AC by performing western blotting and ELISA. The expression levels of miR‑31 were significantly decreased in the nasal mucosa of the AR group compared with those in the control group. Moreover, upregulation of miR‑31 markedly attenuated sneezing and nasal rubbing events, reduced nasal eosinophil infiltration and goblet cell hyperplasia, and decreased the levels of OVA‑specific IgE and Th2‑related cytokines. In addition, subsequent in vitro experiments showed that upregulation of miR‑31 inhibited IL‑13 receptor α1 chain expression and signal transducer and activator of transcription 6 phosphorylation in NECs. Furthermore, miR‑31 suppressed IL‑13‑induced expression of thymic stromal lymphopoietin, granulocyte‑macrophage colony‑stimulating factor, eotaxin and mucin 5AC in NECs. In conclusion, these data revealed that miR‑31 could ameliorate AR by suppressing IL‑13‑induced nasal epithelial inflammatory responses, and thus may serve as a novel therapeutic target for AR.

Topics: Adult; Animals; Case-Control Studies; Disease Models, Animal; Down-Regulation; Epithelial Cells; Female; Gene Expression Regulation; Humans; Immunoglobulin E; Interleukin-13; Male; Mice; Mice, Inbred BALB C; MicroRNAs; Middle Aged; Mucin 5AC; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Young Adult

The objective of this study was to evaluate the effects of allergic rhinitis (AR) on the development, progression, and recovery of acute otitis media (OM) in an animal model and investigate the secondary effects of bacterial infection.. BALB/c mice were divided into four groups: AR + OM, AR, OM, and control groups. AR + OM and AR groups were sensitized with ovalbumin (OVA) and alum and then challenged intranasally with OVA. Phosphate-buffered saline (PBS) was administered to the OM and control groups the same number of times. After AR induction, OM was induced by surgical inoculation of non-typeable Haemophilus influenza (NTHi) into the middle ear (ME) cavity of the mice in the AR + OM and OM groups. PBS was injected into the bulla in the AR and control groups. Each group was subdivided into sets of six mice, one for each of the four time points (0, 2, 7, and 10 days post-bacterial inoculation), at which point the mice were euthanized and ME and nasal cavity mucosa were obtained and evaluated. The occurrence of OM and the ME mucosa thickness were evaluated and compared among the four groups. Tissue expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in infected ME mucosa was assessed by immunohistochemical staining. We also investigated IgE, IL-4, and IL-5 in the nasal mucosa.. Most of the ears showed OM on post-inoculation day 2 in both AR + OM and OM groups. In the AR + OM group, 58.3% of ears still had OM on post-inoculation day 10, while only 16.7% of the OM group had OM. The ME mucosa of all groups increased, and the AR + OM group exhibited the thickest mucosa. The OM group showed peak thickness on post-inoculation day 2 and then decreased, whereas the ME mucosa thickness of the AR + OM group continued to increase to day 7. In the OM group, the expression of IL-1β, IL-6, and TNF-α in the ME also increased significantly, peaking on post-inoculation day 2, and then gradually decreased. In the AR + OM group, the expression of these proteins increased until day 7 and then decreased. The IgE and Th2 response (IL-4 and IL-5) cytokines were expressed at higher levels in the AR + OM and AR groups than in the OM and control groups.. The inflammatory reaction to NTHi was more intense and lasted longer in the allergic group, which indicates that AR affects the progression and subsequent recovery of acute bacterial OM.

Topics: Animals; Cytokines; Disease Models, Animal; Mice; Mice, Inbred BALB C; Nasal Mucosa; Otitis Media; Ovalbumin; Rhinitis, Allergic

It was reported that the expression of Toll-like receptor (TLR) 9 may be related to Th2-type allergic inflammation including allergic rhinitis (AR). However, little is known about the expression of TLR9 in the basophils in AR. In the present study, the expression of TLR9 was examined by flow cytometry analysis, and the expression of TLR9 mRNA in KU812 was determined by quantitative real-time PCR. The results showed that the percentage of TLR9

Topics: Adult; Allergens; Animals; Basophils; Cell Line; Disease Models, Animal; Female; Flow Cytometry; Gene Expression Regulation; Granulocytes; HLA-DR Antigens; Humans; Immunoglobulin E; Interleukin-13; Interleukin-6; Male; Mice; Mice, Inbred BALB C; Middle Aged; Ovalbumin; Pollen; Pyroglyphidae; Rhinitis, Allergic; RNA, Messenger; Toll-Like Receptor 9; Up-Regulation; Young Adult

Allergic rhinitis (AR) is an IgE-mediated chronic inflammatory disease of the allergic nasal mucosa. It has a significant effect on quality life; most patients with AR also suffer from sleep disorders, mood disorders, and deterioration in social relationships. As increasing numbers of medicinal plants show productive anti-inflammatory activity against inflammatory diseases, there is growing interest in natural medicinal plant ingredients. To this end, we selected

Topics: Animals; Astragalus Plant; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Nod2 Signaling Adaptor Protein; Ovalbumin; Polysaccharides; Rats; Rhinitis, Allergic; Transcription Factor RelA

Several factors, including bacterial and viral infections, have been associated with rhinosinusitis and nasal tissue remodelling that may result in nasal polyp formation. However, the potential role of bacterial or viral stimuli triggering polyp development is unclear. Here, we used lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid [poly(I:C)] in a murine model of allergic rhinosinusitis to compare different effects of bacterial- and virus-derived stimuli in the pathogenesis of nasal polyp formation. Briefly, BALB/c mice were sensitised and challenged with ovalbumin and staphylococcal enterotoxin, with or without LPS or poly(I:C), and the consequent histopathological profiles, cytokines, and systemic humoral responses were studied. While no significant differences in polyp formations and epithelial disruptions were observed among the experimental groups, the local cell recruitment patterns slightly differed in animals that received either LPS or poly(I:C). Additionally, the local immune environments generated by LPS or poly(I:C) stimulation varied. LPS stimulation induced a marked Th1/Th17 response and predominantly neutrophilic nasal polyp formations, whereas poly(I:C) induced a Th2-skewed environment in neutrophilic nasal polyp development. Overall, our findings show that both cell recruitment patterns and local immune environments induced by these two stimuli differ, which may have implications in the physiopathology of rhinosinusitis with nasal polyp.

Topics: Animals; Cytokines; Disease Models, Animal; Enterotoxins; Humans; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Nasal Mucosa; Nasal Polyps; Neutrophils; Ovalbumin; Poly I-C; Rhinitis, Allergic; Sinusitis; T-Lymphocyte Subsets

Cordyceps militaris has been widely studied for its various pharmacological activities such as antitumor, anti-inflammation, and immune regulation. The binding of an allergen to IgE-sensitized mast cells in nasal mucosa triggers allergic rhinitis. We found that oral administration of 300 mg/kg of the ethanol extract prepared from silkworm pupa-cultivated Cordyceps militaris fruiting bodies significantly alleviated the symptoms of ovalbumin-induced allergic rhinitis in mice, including sneeze/scratch, mast cell activation, eosinophil infiltration, and Syk activation. The treatment of ethanol extract significantly suppressed the release of β-hexosaminidase (a degranulation marker) and mRNA expression levels of various cytokines, including IL-3, IL-10, and IL-13 in activated RBL2H3 cells. The ethanol extract and β-sitostenone, which was purified from the extract, could respectively reduce the Ca

Topics: Animals; Anti-Allergic Agents; Bombyx; Calcium Signaling; Cell Degranulation; Cell Line, Tumor; Cordyceps; Cytokines; Disease Models, Animal; Ethanol; Fruiting Bodies, Fungal; Larva; Male; Mast Cells; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rats; Rhinitis, Allergic; Solvents

Ozone (O. Sprague-Dawley (SD) rats were sensitized and challenged with ovalbumin (OVA) to make AR models. Three groups of AR rats were exposed respectively to 0.5, 1.0, 2.0 ppm of O. The combination of allergen and repeated O. O

Topics: Administration, Inhalation; Animals; Cytokines; Disease Models, Animal; Eosinophilia; Eosinophils; Female; Immunoglobulin E; Inflammation; Inflammation Mediators; Nasal Mucosa; Ovalbumin; Ozone; Rats, Sprague-Dawley; Rhinitis, Allergic; Th2 Cells

The work aimed to develop a co-loaded loratadine and sulpiride nasal nanoemulsion for allergic rhinitis management.. Compatibility studies were conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. Nanoemulsion formulations were prepared using soybean lecithin, olive oil and tween 80. Sodium cholate and glycerol were employed as co-surfactants. Nanoemulsions were assessed for viscosity, pH, droplet size, polydispersity index, zeta potential, electrical conductivity, entrapment,. Compatibility studies revealed absence of drug/drug interactions. Nanoemulsions exhibited > 90% entrapment efficiency. The selected nanoemulsion demonstrated small droplet size (85.2. The results reflected a promising potent effect of the combined loratadine and sulpiride nasal nanoemulsion in managing the symptoms of allergic rhinitis.

Topics: Administration, Intranasal; Animals; Calorimetry, Differential Scanning; Disease Models, Animal; Dopamine Antagonists; Drug Combinations; Drug Liberation; Emulsions; Glycerol; Glycine max; Histamine H1 Antagonists, Non-Sedating; In Vitro Techniques; Interleukin-1; Lecithins; Loratadine; Nanostructures; Nasal Mucosa; Olive Oil; Ovalbumin; Paranasal Sinuses; Polysorbates; Rabbits; Rhinitis, Allergic; Sodium Cholate; Spectroscopy, Fourier Transform Infrared; Sulpiride; Surface-Active Agents; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Emerging evidence shows that circular RNAs (circRNAs) participate in the pathogenesis of multiple immune diseases. However, few studies have focused on the mechanisms of circRNAs involved in allergic rhinitis (AR).. This study performed an RNA sequence (RNA-seq) profiling to identify the expression of circRNAs in nasal mucosa from ovalbumin-induced AR murine models and normal controls. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) was then conducted to validate the differential expression of circRNAs. Bioinformatics analysis was applied to demonstrate the biological functions of the dysregulated circRNAs.. A total of 86 distinct circRNA candidates were sequenced, of which 51 were upregulated and 35 were downregulated. The T cell receptor, B cell receptor, and calcium signaling pathways may be involved in the pathology of AR. Furthermore, a circRNA-miRNA interaction network was constructed via miRNA response elements analysis. Some circRNAs were correlated with miRNAs that are involved in T cell polarization and activation, thereby highlighting their potential role in the pathogenesis of AR.. This study demonstrates a number of aberrantly expressed circRNAs related to AR, and offers a novel perspective into AR pathogenesis and future therapeutic strategies.

Topics: Animals; Computational Biology; Disease Models, Animal; Down-Regulation; Gene Regulatory Networks; Humans; Male; Mice; MicroRNAs; Ovalbumin; Real-Time Polymerase Chain Reaction; Rhinitis, Allergic; RNA-Seq; RNA, Circular; Up-Regulation

Allergic rhinitis (AR) is a ubiquitous chronic disease with a growing incidence. We aimed to investigate the protective effect of naringenin against AR induced in rats.. Thirty-two Sprague Dawley rats were divided into four groups of eight animals each. Group 1 represented the control group. The other 24 rats were sensitized with intraperitoneal 0.3 mg ovalbumin (OVA) and 30 mg aluminum hydroxide every other day for 14 days to induce AR. Ten microliters OVA was administered to both nostrils by inhalation for the following seven days to provoke AR. Group 2 represented the AR group and received no treatment. Group 3 was treated as the reference group and received 5 mg/kg desloratadine every day between days 15 and 21. Group 4 received 100 mg/kg naringenin orally between days 15 and 21. All animal's sneezing and nasal itching scores were recorded on day 22. The rats were then sacrificed. Serum total IgE, IL4 and IL5 values were studied, and nasal structures were extracted 'en bloc' for histopathological examination.. Significant clinical recovery was achieved in the group treated with naringenin. Serum total IgE, IL4 and IL5 values in the naringenin group were significantly lower than in the AR group, and significant histopathological improvement was observed compared to the AR group.. Naringenin produced significant clinical, biochemical and histopathological benefits in rats with induced AR. These effects suggest that naringenin is a promising agent for the treatment of AR.

Topics: Animals; Disease Models, Animal; Flavanones; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic

Histamine derived from mast cells and basophils plays important roles in inducing allergic symptoms. Although T cells also produce histamine, the involvement of the histamine produced from T cells has remained enigmatic. We sought to reveal the roles of T helper 2 (Th2) cell-derived histamine in nasal allergic disorders.. The histamine production from Th2 cells was measured by EIA. The mRNA expression of histidine decarboxylase (HDC) was measured by real-time PCR. To investigate the roles of Th2 cell-derived histamine in vivo, we analyzed an antigen-specific Th2 cell transfer mouse model.. Th2 cells produced histamine by T cell receptor stimulation, and these properties were specific for Th2 cells, but not Th1 cells and naïve CD4 T cells. The histamine produced from Th2 cells was involved in the infiltrations of Th2 cells in response to antigen exposure.. These results suggest that Th2 cell-derived histamine play important roles in nasal allergic disorders.

Topics: Allergens; Animals; Cell Movement; Histamine; Histidine Decarboxylase; Mice, Inbred BALB C; Mice, Knockout; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Th2 Cells

The combined allergic rhinitis and asthma syndrome (CARAS) is a chronic airway inflammation of allergic individuals, with a type 2 immune response. Pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study was to evaluate the synthetic alkaloid, MHTP in the experimental model of CARAS. Therefore, BALB/c mice were ovalbumin (OVA) -sensitized and -challenged and treated with MHTP by intranasal or oral routes. Treated animals showed a decrease (p < 0.05) of sneezing, nasal rubbings, and histamine nasal hyperactivity. Besides, MHTP presented binding energy and favorable interaction for adequate anchoring in the histamine H1 receptor. MHTP treatment inhibited the eosinophil migration into the nasal (NALF) and the bronchoalveolar (BALF) fluids. Histological analysis showed that the alkaloid decreased the inflammatory cells in the subepithelial and perivascular regions of nasal tissue and in the peribronchiolar and perivascular regions of lung tissue. The MHTP treatment also reduced the pulmonary hyperactivity by decreasing the smooth muscle layer hypertrophy and the collagen fiber deposition in the extracellular matrix. The immunomodulatory effect of the alkaloid was due to the decrease of cytokines like IL-5 and IL-17A (type 2 and 3), TSLP (epithelial), and the immunoregulatory cytokine, TGF-β. These MHTP effects on granulocytes were dependent on the p38/ERK1/2 MAP kinase signaling pathway axis. Indeed, the synthetic alkaloid reduced the frequency of activation of both kinases independent of the NF-κB (p65) pathway indicating that the molecule shut down the intracellular transduction signals underlie the cytokine gene transcription.

Topics: Allergens; Animals; Anti-Asthmatic Agents; Asthma; Cytokines; Disease Models, Animal; Female; Humans; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Ovalbumin; p38 Mitogen-Activated Protein Kinases; Receptors, Histamine H1; Rhinitis, Allergic; Tetrahydroisoquinolines

Bone marrow mesenchymal stem cells (BMSCs) have immunomodulatory and therapeutic effects on immune system diseases. This study intends to assess the regulatory effect of BMSC targeted therapy on the IL-17+ γδ T cells and Treg cells in allergic rhinitis (AR).. BALB/c mice were sensitized by ovalbumin (OVA), while BMSCs were injected intravenously before sensitization and followed by an analysis of nasal symptoms, inflammation, cytokines, and immunoglobulins. BMSCs were co-cultured with peripheral blood mononuclear cells for 3 days to test Foxp3+ expression, IL-17+ γδ T and Foxp3+Treg cell ratio, and cytokines secretion.. After intranasal administration of BMSCs, nasal symptoms and inflammatory infiltration in mice were significantly alleviated, accompanied by reduced OVA-specific IgE in serum. BMSCs significantly inhibited the activity of T lymphocytes, increased TGF-β1 level, decreased IL-17A level, promoted Treg proliferation, and suppressed the proliferation of IL-17+ γδ T cells.. BMSC targeted therapy can be used to treat AR by regulating Treg cells to correct IL-17+γδ T cell immune imbalance and is expected to be an effective treatment method for AR.

Topics: Animals; Cells, Cultured; Disease Models, Animal; Injections, Intraperitoneal; Interleukin-17; Mesenchymal Stem Cells; Mice; Ovalbumin; Receptors, Antigen, T-Cell, gamma-delta; Rhinitis, Allergic; T-Lymphocytes, Regulatory

Most allergic disease studies have focused on postnatal chemical or microbial exposure. Recent studies have indicated that allergic diseases are associated with the immunological interaction between the mother and her offspring, but the relevant mechanisms are unclear. The aim of this study was to assess whether maternal exposure to allergens during pregnancy could affect allergic rhinitis (AR) in the offspring. Compared with offspring of naïve mothers, offspring of ovalbumin (OVA)-exposed mothers exhibited a significant reduction in AR clinical symptoms and levels of histamine, IgE, T helper type-2(Th2) cytokines, thymic stromal lymphopoietin, cyclooxygenase-2, chemokines, infiltration of inflammatory cell, and activity of caspase-1. Interestingly, we observed that offspring of OVA-exposed mothers regulated OVA-induced Th2 responses by inducing autophagy in mast cells. Our data demonstrated that maternal exposure to OVA during pregnancy decreased allergic sensitivity in offspring, suggesting that the vertical transmission of maternal immune responses may be involved. These findings have important implications in the regulation of AR. Furthermore, we propose that the autophagy of mast cells may be a potential target for AR prevention or treatment.

Topics: Allergens; Animals; Autophagy; Disease Models, Animal; Female; Histamine; Humans; Immunity, Maternally-Acquired; Immunoglobulin E; Mast Cells; Maternal Exposure; Mice; Mice, Inbred BALB C; Ovalbumin; Pregnancy; Prenatal Exposure Delayed Effects; Rhinitis, Allergic; Th2 Cells

We aimed to investigate the therapeutic effects of melatonin in an experimental AR model.. Thirty-two Wistar rats were randomised into four groups (n = 8 each). The experimental AR model was established in the saline (SF), ethanol, and melatonin groups via intraperitoneal (i.p.) injections and intranasal application of ovalbumin. The SF, ethanol, and melatonin groups received daily i.p. saline, 2% ethanol dissolved in saline, and 10 mg/kg melatonin dissolved in 2% ethanol and saline. The control group received the same amount of i.p. and intranasal saline. Total nasal symptom scores were recorded in all rats on days 1 (baseline), 15, 20, 25, and 30. Serum ovalbumin-specific IgE, IL-13, and melatonin levels were measured on days 1 (baseline), 15, and 30. The nasal mucosa of all rats was scored histopathologically.. The total nasal symptom scores and serum ovalbumin-specific IgE values of the SF, ethanol, and melatonin groups were significantly higher on day 15 than those of the control group. On day 30, the scores and serum ovalbumin-specific IgE values of the melatonin group were similar to those of the control, whereas the SF and ethanol groups had statistically higher scores. The histological scores of the SF and ethanol groups were significantly higher than those of the control and melatonin groups, but no significant difference was found between the melatonin and control groups.. Melatonin reduced total nasal symptom scores and serum ovalbumin-specific IgE levels and improved histological inflammation parameters in the ovalbumin-induced rat experimental AR model.

Topics: Aluminum Hydroxide; Animals; Antioxidants; Disease Models, Animal; Goblet Cells; Immunoglobulin E; Interleukin-13; Male; Melatonin; Nasal Mucosa; Ovalbumin; Random Allocation; Rats; Rats, Wistar; Rhinitis, Allergic; Symptom Assessment

The objective of the study is to evaluate the protective effects of human mesenchymal stem cells (hMSCs) modified with miR-138-5p inhibitor against the allergic rhinitis and asthma syndrome (ARAS). MiR-138-5p or negative control was transfected into hMSCs, and fluorescence-activated cell sorting was used to evaluate hMSC surface markers. Quantitative real-time PCR (qRT-PCR) was used to evaluate miR-138-5p, SIRT1, caspase-3, IL-6, IL-1β and TNF-α levels after TNF-α and IL-6 stimulations. hMSCs with or without miR-138-5p inhibition was intranasally administered into ARAS mice (n = 10 each group), followed by monitoring sneezing and nasal rubbing events to evaluate the allergic symptoms. Histamine, ovalbumin-specific IgE, IgG2a, IgG1 and LTC4 release were monitored in the serum and nasal lavage fluid using enzyme-linked immunosorbent assay. Expression of SIRT1 and HMGB1/TLR4 pathway in nasal mucosa was assessed. After miR-138-5p inhibitor transfection, the hMSC lineage was preserved. Binding between SIRT1 and miR-138-4p was observed, and miR-138-5p inhibition led to upregulation of SIRT1. Inhibition of miR-138-5p led to attenuated inflammatory responses of hMSCs upon TNF-α and IL-6 stimulation, and allergic symptoms in mice, as well as histamine and ovalbumin-specific IgG release. hMSCs with miR-138-5p inhibition showed characteristics of activated SIRT1 and inhibited HMGB1/TLR4 pathway. Inhibition of miR-138-5p in hMSCs enhanced its effects in attenuating inflammatory responses and allergic reaction in the ARAS model, which is presumably regulated by SIRT1 and the HMGB1/TLR4 pathway.

Topics: Animals; Apoptosis; Asthma; Cell Proliferation; Cells, Cultured; Cytokines; Female; HMGB1 Protein; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; MicroRNAs; Ovalbumin; Protective Agents; Rhinitis, Allergic; Sirtuin 1

The circRNAs-miRNAs-mRNAs competing endogenous RNA (ceRNA) networks involve in regulating the development of various inflammation-associated diseases, including allergic rhinitis (AR), and the present study aimed to identify novel AR-associated ceRNA networks.. The mRNA and protein levels of the associated genes were, respectively, examined by real-time qPCR and western blot analysis. The targeting sites in miR-556-5p and NLRP3 were validated by performing dual-luciferase reporter gene system assay. ELISA was used to measure inflammatory cytokines secretion, and CCK-8 assay was conducted to determine cell proliferation.. Here, we first identified a hsa_circ_0000520/miR-556-5p/NLRP3 signaling cascade triggered epithelium pyroptosis and inflammation to regulate the development of AR in cellular and mice models. Specifically, the pyroptosis-associated biomarkers (NLRP3, ASC, IL-1β and IL-18) and pro-inflammatory cytokines (OVA-specific IgE, TNF-α, IL-4 and IL-5) were upregulated in the nasal subjects collected from AR patients and ovalbumin (OVA)-induced AR mice models, compared to their normal counterparts. Next, using the ceRNA networks analysis software, we screened out a hsa_circ_0000520/miR-556-5p axis that potentially regulated NLRP3 in the human nasal epithelial cell line. Mechanistically, miR-556-5p targeted both hsa_circ_0000520 and 3' untranslated region (3'UTR) of NLRP3, and knock-down of hsa_circ_0000520 inactivated NLRP3-mediated epithelium pyroptosis through miR-556-5p in a ceRNA-dependent manner. Furthermore, we proved that both hsa_circ_0000520 ablation and miR-556-5p overexpression suppressed NLRP3-mediated cell pyroptosis to attenuate AR in mice models.. Taken together, we evidenced that targeting the hsa_circ_0000520/miR-556-5p/NLRP3 signaling pathway was a novel AQ1strategy to ameliorate AR progression; however, future clinical data are still required to validate our preliminary results.

Topics: Adolescent; Adult; Allergens; Animals; Cell Line; Cytokines; Disease Models, Animal; Female; Humans; Male; MicroRNAs; Middle Aged; Nasal Mucosa; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Pyroptosis; Rhinitis, Allergic; RNA, Circular; Signal Transduction; Young Adult

Ginseng (the root of

Topics: Animals; Cytokines; Disease Models, Animal; Fermented Foods; Immunoglobulin E; Inflammation; Interleukin-4; Mice; Mice, Inbred BALB C; Ovalbumin; Panax; Rhinitis, Allergic

Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Carrier Proteins; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Eosinophils; Guinea Pigs; Histamine; Immunoglobulin E; Mast Cells; Mice; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Th1 Cells; Th1-Th2 Balance; Th2 Cells

Allergic rhinitis (AR) is a common chronic respiratory disease. Asarum heterotropoides (AH) is predicted to be a treatment for allergic diseases, but its therapeutic effect is unclear. We aimed to determine the anti-allergic effects of AH in mice with ovalbumin (OVA)-induced AR. OVA-induced AR mouse model was constructed, and AH was orally administered for a week; next, nasal clinical symptoms were evaluated. The levels of serum histamine, OVA-specific IgE, and IL-13 were measured by ELISA. Inflammatory cells, including leukocytes, neutrophils, eosinophils, and macrophages were counted in the nasal lavage fluid (NALF). Histopathological examinations of the nasal tissues were performed using H&E, Giemsa, and PAS staining. The production of periostin and eotaxin-3 from AH-treated human nasal epithelial cells (HNEpCs) in vitro, was measured using ELISA. Oral administration of AH alleviated allergic symptoms in mice with AR; significantly decreased levels of allergic mediators, such as serum histamine and OVA-specific IgE. The decrease in allergic symptoms positively correlated with the decrease in serum allergic mediators. The NALF of AH-treated AR mice demonstrated lower number of eosinophils. AH demonstrated a capacity to reduce the infiltration of mast cells, eosinophils, and goblet cells, thereby resulting in thinner nasal tissues. Moreover, treatment of HNEpCs with AH demonstrated suppressed production of periostin and eotaxin-3. AH exerts a therapeutic effect in modulating AR through multi-target and multi-function influence on regulating B cells, mast cells, eosinophils, goblet cells, and epithelial cells.

Topics: Animals; Anti-Allergic Agents; Asarum; Disease Models, Animal; Female; Humans; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Rhinitis, Allergic

Topics: Adolescent; Adult; Animals; Apoptosis; Female; Humans; Inflammation; Janus Kinase 1; Leukemia Inhibitory Factor; Mice; Mice, Inbred BALB C; MicroRNAs; Middle Aged; Ovalbumin; Rhinitis, Allergic; RNA Interference; RNA, Long Noncoding; STAT3 Transcription Factor; Up-Regulation; Young Adult

This study examined the potential roles of CC10 (Clara cell 10-kD protein) and ILC2s (type 2 innate lymphoid cells) in allergic rhinitis (AR). After ovalbumin was used to construct the AR model, microarray analysis was performed to reveal the key differentially expressed genes. The phenotypic changes of nasal mucosa were examined by H&E staining. Western blot analysis, qRT-PCR, ELISA and immunohistochemistry were performed to identify the levels of cytokines. The lineage markers (CD127 and CD117) of ILC2s were detected using immunofluorescence. The microarray analysis and qRT-PCR results showed that CC10 overexpression inhibited the expression of A20, BAFF, and IL-4 R

Topics: Animals; Biomarkers; Cytokines; Disease Models, Animal; Down-Regulation; Female; HEK293 Cells; Humans; Immunity, Innate; Lymphocyte Activation; Lymphocytes; Mice; Mice, Inbred C57BL; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Signal Transduction; Transfection; Up-Regulation; Uteroglobin

Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear.. To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims.. Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism.. In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes.. Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.

Topics: Allergens; Animals; Anti-Allergic Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Artemisia; Candida glabrata; Cytokines; Edema; Escherichia coli; Guinea Pigs; Male; Medicine, Chinese Traditional; Medicine, Mongolian Traditional; Mice; Molecular Docking Simulation; Nasal Mucosa; Ovalbumin; Plant Extracts; Receptors, Histamine H1; Rhinitis, Allergic; Sinusitis; Staphylococcus aureus; Xylenes

Topics: Animals; Cytokines; Disease Models, Animal; Immunoglobulin E; Immunoglobulin G; Inflammation; Interleukin-17; Interleukin-6; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-kappa B; Nuclear Receptor Subfamily 1, Group F, Member 3; Oleanolic Acid; Ovalbumin; Rhinitis, Allergic; Saponins; Signal Transduction; STAT3 Transcription Factor; Th17 Cells; Th2 Cells

Allergic rhinitis (AR) is a common disease that causes severe inflammation and even disabilities. Previous studies have reported baicalein to have an anti-inflammatory effect. However, the pharmacological action of baicalein on anaphylaxis has not been clarified yet. This study assessed the in vivo protective effect of baicalein post-treatment in an ameliorating ovalbumin (OVA)-sensitized AR rat model. Baicalein attenuated histological alterations, aberrant tissue repair and inflammation after OVA-induced AR. Baicalein reduced the frequency of nasal/ear rubs and sneezes in rats, and inhibited generation of several inflammatory cytokines (TNF-α, IL-1β, and IL-6) in both blood and nasal lavage of rats. Infiltrations of eosinophils, lymphocyte, and neutrophils were decreased in baicalein-administered rats. Furthermore, baicalein inhibited the expression of STAT3 phosphorylation in the nasal mucosa. In summary, baicalein attenuated OVA-induced AR and inflammation, which suggests it as a promising therapeutic agent for the alleviation of AR-associated inflammation and pathology.

Topics: Animals; Disease Models, Animal; Eosinophils; Flavanones; Inflammation; Lymphocytes; Male; Nasal Mucosa; Ovalbumin; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic

Allergic rhinitis (AR) is a worldwide highly prevalent nasal inflammatory disease with elusive mechanisms about the regulation of innate immune response. The roles and mechanisms of NLRP3, a typical inflammasome, in AR development remain unclear. Here we investigate the roles of NLRP3 inflammasome activation in the development and progression of AR and try to uncover its potential mechanisms underlying. Wildtype and NLRP3 knockout mice were applied to construct the ovalbumin (OVA)-induced AR model. Caspase-1 specific inhibitor Belnacasan and inflammasome activator ATP were used for adjuvant stimulation of AR-model mice respectively. We found that the production of IL-1β and the activation of inflammasome were increased in both patients and mice with AR. NLRP3 deficiency markedly suppressed AR progression with reduced inflammatory response and epithelium pyroptosis in mice with AR. Furthermore, Caspase-1 inhibitor treatment in vivo ameliorated the development and progression of AR with favorable outcomes. Mechanistically, inflammation augments and nasal mucosa injury during AR were partially due to ASC-specks accumulation and subsequent cell pyroptosis. Our study reveals the previously unknown roles of NLRP3 inflammasome in promoting the development and progression of AR via enhancing inflammatory response and epithelium pyroptosis and thus provides a potential clue for allergic disease interventions.

Topics: Adolescent; Adult; Aged; Animals; Cell Line; Disease Progression; Epithelium; Female; Humans; Immunoglobulin E; Inflammasomes; Inflammation; Interleukin-1beta; Male; Mice; Middle Aged; Nasal Mucosa; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Pyroptosis; Rhinitis, Allergic; Young Adult

Increased epithelial permeability has been reported in allergic rhinitis, with histamine and type-2 inflammation being responsible for tight junction dysfunction. The impact of an epithelial barrier defect on allergic sensitization and mast cell (MC) degranulation remains speculative.. Transepithelial passage of allergens was evaluated on primary human nasal epithelial cell cultures. Active sensitization was attempted by repeated intranasal ovalbumin (OVA) applications in Naïve mice. In a passive sensitization model, mice were injected with IgE to Dermatophagoides pteronyssinus (rDer p)2 and then exposed intranasally to the allergen. Chitosan was used to disrupt nasal epithelial integrity in vitro and in vivo.. Chitosan strongly reduced transepithelial electrical resistance and facilitated transepithelial allergen passage in cultured primary nasal epithelial cells. In vivo, intranasal chitosan affected occludin expression and facilitated allergen passage. After epithelial barrier disruption, intranasal OVA application induced higher OVA-specific IgG1 and total IgE in serum, and increased eosinophilia and interleukin-5 in bronchoalveolar lavage (BAL) compared to sham-OVA mice. Chitosan exposure, prior to rDer p2 allergen challenge in passively sensitized mice, resulted in increased β-hexosaminidase levels in serum and BAL compared to sham-rDer p2 mice. Intranasal treatment with the synthetic glucocorticoid fluticasone propionate prevented chitosan-induced barrier dysfunction, allergic sensitization, and MC degranulation.. Epithelial barrier dysfunction facilitates transepithelial allergen passage, allergic sensitization, and allergen-induced MC degranulation even in the absence of inflammatory environment. These results emphasize the crucial role of an intact epithelial barrier in prevention of allergy.

Topics: Allergens; Animals; Cell Degranulation; Inflammation; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic

The CC chemokine receptor 3 (CCR3) expressed by eosinophils, mast cells and Th2 cells is closely related to allergic diseases. The objective of this study was to explore whether silencing of CCR3 with short hairpin RNAs (shRNAs) delivered by a lentiviral vector could impact the function of mast cells in a murine model of allergic rhinitis (AR) in vivo. The murine model of allergic rhinitis (AR) inducing by ovalbumin (OVA) was constructed, and the BALB/c mice were divided into normal control group, AR group, controlshRNA treated group and lentiviral CCR3-shRNA treated group. The recombinant lentivirus vectors which express a short hairpin RNA (shRNA) targeting the CCR3 were dropped into the nasal cavity of OVA-sensitized mice before the challenges. Real-time fluorescence quantitative PCR and western blotting were performed to observe inhibitory effect of CCR3 gene. Nasal symptoms of mice and OVA-specific IgE in each group were assessed. Concentrations of histamine, tryptase and Prostaglandin D2 (PGD2) in bone marrow, peripheral blood and nasal mucosa were analyzed. Furthermore, histological analysis and electron microscopy analysis were applied to detect the histology changes of nasal mucosa and the infiltration of mast cells in nasal mucosa. The results showed that administration of CCR3shRNA could effectively inhibit the expression of the CCR3 gene in bone marrow, peripheral blood and nasal mucosa, which reduced the nasal symptoms, the level of OVA-specific IgE, the inflammatory cells and mast cells infiltration into nasal cavity, and relieved the histopathological changes of nasal mucosa. In addition, intervention of CCR3shRNA could reduce the levels of the histamine, tryptase and PGD2 in bone marrow, peripheral blood and nasal mucosa. These results suggest that inhibition of CCR3 gene expression by shRNAs lentiviral vectors can effectively attenuate migration, infiltration and degranulation of mast cells in local tissues and alleviate the inflammation of allergic rhinitis mice.

Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Animals; Bone Marrow; Cell Degranulation; Cell Movement; Disease Models, Animal; Humans; Lentivirus; Male; Mast Cells; Mice; Microscopy, Electron; Nasal Mucosa; Ovalbumin; Receptors, CCR3; Rhinitis, Allergic; RNA Interference; RNA, Small Interfering

Ten-eleven-translocation (Tet) proteins are 5-methylcytosine oxidases and have profound impact on DNA methylation and genes expression. This study aimed to investigate the role of Tet2 and its association with Foxp3 DNA methylation in regulatory T (Treg) cell of allergic rhinitis (AR).. CD4. Treg cells drawn from AR patients and OVA-exposed mice showed reduction in cells counts, expression of Foxp3 mRNA and protein and down-regulation of Tet2, compared with the controls. Hypermethylation of Foxp3 TSDR and decline of TET2 binding to Foxp3 TSDR, but not promoter, were noted in Treg cells of OVA-exposed mice. Significant negative correlations between Tet2 expression and Foxp3 TSDR methylation, Foxp3 TSDR methylation and Foxp3 expression, and positive correlation between Foxp3 expression and Treg cells percentage were demonstrated by correlation analysis.. This study demonstrated that down-regulation of Tet2 was associated with higher methylation level of Foxp3 TSDR, reduction in Foxp3 expression and Treg cells percentage in AR, suggesting that Tet2 probably modulated the function of Treg cells in AR through Foxp3 methylation.

Topics: Adolescent; Adult; Aged; Animals; Case-Control Studies; Dioxygenases; Disease Models, Animal; DNA Methylation; DNA-Binding Proteins; Down-Regulation; Female; Forkhead Transcription Factors; Gene Expression Regulation; Humans; Immunoglobulin E; Mice, Inbred C57BL; Middle Aged; Nasal Mucosa; Ovalbumin; Proto-Oncogene Proteins; Rhinitis, Allergic; T-Lymphocytes, Regulatory

The G protein-coupled estrogen receptor (GPER) specific agonist G-1 has therapeutic effects in patients with allergic diseases, but any role for G-1 as a therapy for inflammation associated with allergic rhinitis (AR) remains unclear. The structure of the environmental hormone nonylphenol (NP) is very similar to that of estrogen; it binds to the estrogen receptor to produce estrogen-like effects and thus may also bind to the membrane GPER. We explored whether NP administration would reduce the effects of G-1 on AR, the interactions between the two materials, and their mechanisms of action using a murine model of AR. Mice were randomly assigned into control, AR, G-1, and G-1 + NP groups (n = 10/group). AR nasal symptoms were scored. Eosinophils in nasal mucosa were counted after staining with hematoxylin and eosin. Serum ovalbumin (OVA)-specific IgE was determined by ELISA. The proportions of splenic Th1, Th2, and Treg cells were determined by flow cytometry. The expression of transcription factors unique to Th1, Th2, Treg cells and cytokine levels in nasal mucosa were evaluated by real-time PCR and cytometric bead arrays. AR nasal symptoms, including sneezing, nasal scratching, eosinophil infiltration of nasal mucosa, and serum IgE, were reduced in G-1 group. After injection, Th2 cells proportions, Th2-immune response-related cytokines (IL-4, IL-5, and IL-13), and a Th2 cell-specific transcription factor (GATA-3) were significantly decreased in G-1 group. Treg immune response was enhanced (as reflected by Treg cell, IL-10, and Foxp3 levels). The levels of all of these were significantly increased after adding NP, and the Treg immune response was significantly decreased. These results indicate that G-1 attenuated the nasal symptoms, serum OVA-specific IgE, and Th2 cell immune response, whereas it enhanced Treg immune response, in mice with AR. Adding NP weakened these therapeutic effects.

Topics: Animals; Cyclopentanes; Disease Models, Animal; Drug Interactions; Endocrine Disruptors; Estrogens; Female; Humans; Mice; Nasal Mucosa; Ovalbumin; Phenols; Quinolines; Receptors, Estrogen; Receptors, G-Protein-Coupled; Rhinitis, Allergic; T-Lymphocytes, Regulatory; Th2 Cells

BACKGROUND CircRNAs are involved in multiple biological processes, especially when they act as sponges of miRNA. Thus, the present study investigated the effect of circDdx17 on allergic rhinitis (AR) in an animal model, and determined the miRNA that was involved in this effect. MATERIAL AND METHODS The AR model was created by repetitive stimulation of ovalbumin (OVA). The levels of mRNAs in plasma were determined by qPCR. CircDdx17 stability was assessed using RNase R. The interaction between circDdx17 and miR-17-5p was predicted by bioinformatics and confirmed by dual luciferase assay. Moreover, the frequencies of rubbing and sneezing and pathological changes were recorded, and OVA-specific IgE, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, and IL-5 levels were detected by ELISA. RESULTS Levels of circDdx17 were decreased in OVA-induced AR mice, and miR-17-5p interacted with circDdx17 in spleen cells derived from mice. Moreover, circDdx17 overexpression reduced the expression of miR-17-5p, OVA-specific IgE, TNF-alpha, IL-4, and IL-5, as well as the frequencies of rubbing and sneezing, and alleviated pathological changes in OVA-induced AR mice. CONCLUSIONS CircDdx17 appears to have a protective effect on mice in the progression of AR. Specifically, overexpression of circDdx17 inhibited the expression of miR-17-5p and alleviated the condition of AR. Therefore, circDdx17 appears to be a good candidate for use in prevention of AR. However, the detailed mechanism underlying the circDdx17/miR-17-5p regulatory pathway requires further study.

Topics: Animals; Base Sequence; Female; Gene Expression Regulation; Immunoglobulin E; Inflammation Mediators; Mice, Inbred BALB C; MicroRNAs; Ovalbumin; Protective Agents; Rhinitis, Allergic; RNA, Circular; Spleen

Piper nigrum L. (Piperaceae) is commonly used as a spice and traditional medicine in many countries. It has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the protective role of P. nigrum on epithelial function of upper respiratory tract injury in an allergic rhinitis (AR) mouse model has been unclear. This study aims to investigate the effects of P. nigrum fruit extract (PNE) on the nasal epithelial barrier function of the upper respiratory tract in an ovalbumin (OVA)-induced AR model.. AR mouse model was established by intraperitoneal injection with 200 µL saline containing 50 µg OVA adsorbed to 1 mg aluminum hydroxide, and intranasal challenge with 20 µL per nostril of 1 mg/ml OVA. Besides, mice were orally administrated once daily with PNE and dexamethasone (Dex) in 13 days. The nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokines, nasal histopathology, and immunohistochemistry were evaluated.. The PNE oral administrations inhibited allergic responses via reduction of OVA-specific antibodies levels and mast cells histamine release, accordingly, the nasal symptoms in the early-phase reaction were also clearly ameliorated. In both nasal lavage fluid and nasal tissue, PNE suppressed the inflammatory cells accumulation, specifically with eosinophils. The intravenous Evans blue injection illustrated the epithelial permeability reduction of nasal mucosa layer in PNE-treated mice. Also; PNE treatments protected the epithelium integrity by preventing the epithelial shedding from nasal mucosa; as a result of enhancing the strong expression of the E-cadherin tight junction protein in cell-to-cell junctions, as well as inhibiting the degraded levels of zonula occludens-1 (ZO-1) and occludin into the nasal cavity. Additionally, PNE protected against nasal epithelial barrier dysfunction via enhancing the expression of Nrf2 activated form which led to increasing synthesis of the anti-inflammation enzyme HO-1.. These obtained results suggest that PNE has a promising strategy for epithelial barrier stabilization in allergic rhinitis treatment.

Topics: Animals; Anti-Inflammatory Agents; Heme Oxygenase-1; Male; Membrane Proteins; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-E2-Related Factor 2; Ovalbumin; Piper nigrum; Plant Extracts; Rhinitis, Allergic; Signal Transduction

Farfarae Flos is the dried flower buds of Tussilago farfara L. which is widely used to treat allergic and inflammatory diseases in Chinese folk. Tussilagone (TSL), a sesquiterpene compound purified from Farfarae Flos, has been confirmed the main active component in the plant. However, its anti-allergic activity hasn't been reported yet. The purpose of this study is to investigate the anti-allergic effect of TSL in ovalbumin (OVA)-induced allergic rhinitis (AR) guinea pigs and immunoglobulin E (IgE)-stimulated RBL-2H3 cells. The AR symptoms such as nasal scratching, sneezing and runny nose were scored and the histological changes of nasal mucosa were observed by H&E staining. The levels of histamine, OVA-specific IgE, IL-6 and TNF-α in the serum were measured by ELISA. In IgE-stimulated RBL-2H3 cells, the phosphoryration of Lyn, Syk, Akt, NF-κB p65, ERK and p38 MAPK were investigated by western blot analysis. The results showed that intraperitoneal injection of TSL at doses of 25 and 50 mg/kg significantly alleviated the allergic symptoms and the histological changes of nasal mucosa in OVA-induced allergic rhinitis guinea pigs. Moreover, the levels of histamine, IgE and IL-6 in the serum decreased significantly (p < .05). In vitro, TSL suppressed the phosphorylation of Lyn, Syk, Akt, NF-κB p65, ERK and p38 MAPK in IgE-stimulated RBL-2H3 cells. These results indicate TSL has therapeutic effect on allergic rhinitis in guinea pigs. The anti-allergic mechanism may be through the inhibition of allergic and inflammatory related pathways in mast cells.

Topics: Animals; Anti-Allergic Agents; Cell Line; Drugs, Chinese Herbal; Female; Guinea Pigs; Histamine; Immunoglobulin E; Interleukin-6; Male; Molecular Structure; Nasal Mucosa; Ovalbumin; Phytochemicals; Random Allocation; Rhinitis, Allergic; Sesquiterpenes; Tumor Necrosis Factor-alpha

Allergic rhinitis (AR) is an IgE-mediated inflammation which causes olfactory dysfunction. Antihistamines have been widely used to treat AR while few studies have investigated the effect of antihistamines on improving the sense of smell. In addition, the underlying mechanisms are not well elucidated. We established the ovalbumin (OVA)-induced allergic rhinitis rat model and administrated desloratadine to AR rats. The AR symptoms, serum level of OVA-specific IgE and IL-17, and expression of IL-4, IL-5 and IL-13 in nasal mucosa were measured. The olfactory dysfunction was monitored by buried food test and the expression of GluR1 was measured. Desloratadine treatment alleviated AR symptoms, decreased serum level of OVA-specific IgE and IL-17 in AR rats. Desloratadine decreased IL-4, IL-5, and IL-13 expression in nasal mucosa of AR rats. Desloratadine ameliorated olfactory dysfunction in AR rats and decreased GluR1 expression in AR rats. Desloratadine treatment alleviated AR symptoms and ameliorated olfactory dysfunction in AR rats. The expression of AMPA receptor subunit GluR1 in olfactory bulb was associated with olfactory disorder.

Topics: Animals; Disease Models, Animal; Histamine H1 Antagonists, Non-Sedating; Immunoglobulin E; Interleukins; Loratadine; Nasal Mucosa; Olfaction Disorders; Olfactory Bulb; Ovalbumin; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Rhinitis, Allergic

Nasal obstruction is one of the most bothersome symptoms of allergic rhinitis (AR) affecting sleep-related quality of life in AR patients. Although several treatments were tested to control nasal obstruction, some patients with moderate to severe AR do not respond to current treatments, including the combined administration of different types of anti-allergic medicine. Thus, new options for AR treatment are needed. This study aimed to evaluate the effects of combined treatment with a novel inhibitor of hematopoietic prostaglandin D synthase (HPGDS), TAS-205, and different types of anti-allergic medicine on nasal obstruction in AR. Firstly, we demonstrated that TAS-205 selectively inhibited prostaglandin D

Topics: Acetates; Animals; Anti-Allergic Agents; Cell Line; Cyclopropanes; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Enzyme Inhibitors; Guinea Pigs; Humans; Intramolecular Oxidoreductases; Lipocalins; Male; Morpholines; Nasal Mucosa; Nasal Obstruction; Ovalbumin; Piperidines; Prostaglandin D2; Pyrroles; Quality of Life; Quinolines; Rats; Rhinitis, Allergic; Sulfides; Terfenadine

Allergic rhinitis (AR) is a complex IgE-mediated nasal allergic and inflammatory disease. Nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) is essential in the process of allergic and inflammatory responses. MCC950 is a selective NLRP3 inhibitor. However, its role and mechanism in AR remains undetermined. The present study aimed to explore the effect and mechanism of MCC950 on an ovalbumin (OVA) induced mouse model of AR. The AR BALB/c mice were constructed using OVA and administrated intranasally with MCC950. Concentrations of OVA-specific IgE, histamines and leukotrienes C4 (LTC4) in serum, and OVA-specific IgE, ECP, IFN-γ, IL-4, IL-5, IL-13, IL-1β and IL-18 in nasal lavage fluid (NLF) were assayed by enzyme-linked immunosorbent assay (ELISA). Inflammatory cells were counted in NLF. HE and PAS staing were used for evaluating eosinophils and goblet cells. Immunohistochemistry (IHC) staining were employed to evaluate immunolabeling of NLRP3, Caspase-1, ASC, IL-1β and IL-18 in nasal mucosas of mice. Real-time PCR was conducted to assay NLRP3, Caspase-1, ASC, IL-1β and IL-18 mRNA levels. In vitro studies, western blotting, real-time PCR and ELISA were performed to evaluate the effects and mechanisms of OVA and NLRP3 inhibitor MCC950 on spleen mononuclear cells. We found significant downregulation of sneezing, nasal rubbing, inflammatory cytokines, inflammatory cells and NLRP3, Caspase-1, ASC, IL-1β and IL-18 expression in MCC950 treated mice compared with untreated AR mice. In spleen mononuclear cells culture and stimulation experiment, NLRP3, Caspase-1, ASC, IL-1β and IL-18 levels were upregulated by OVA but inhibited by MCC950. In conclusion, MCC950 could effectively exert its ameliorative effect in murine AR by inhibiting NLRP3 and leads to reduction of Caspase-1, ASC, IL-1β and IL-18, resulting in the attenuation of the allergic and inflammatory responses.

Topics: Allergens; Animals; Anti-Inflammatory Agents; Cells, Cultured; Cytokines; Disease Models, Animal; Female; Furans; Heterocyclic Compounds, 4 or More Rings; Humans; Immunoglobulin E; Indenes; Inflammasomes; Leukocytes, Mononuclear; Mice; Mice, Inbred BALB C; Nasal Mucosa; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Rhinitis, Allergic; Sulfonamides; Sulfones

Allergic rhinitis (AR) is a global health problem and closely related to environmental factors. Ursolic acid (UA) has potential in the treatment of allergic inflammation. The effects of UA intervention on PM2.5-induced AR remain uncertain.. To assess the effects of UA on nasal symptoms and the expression of T-helper (Th)1-Th2-related cytokines in a rat model of AR after fine particulate matter (particulate matter ≤ 2.5 µm [PM2.5]) exposure.. A total of 40 healthy female Sprague-Dawley rats were randomly divided into 4 groups: normal control group (NC group), ovalbumin (OVA)- induced AR model (AR group), PM2.5-exposed AR group exposed to 200 g/m. PM2.5 significantly increased the number of sneezes and nasal rubs in the rats with AR, and UA alleviated these symptoms. UA decreased interleukin (IL)-4, IL-5, IL-13, Eotaxin-1, and OVA Immunoglobulin E (IgE) protein levels. In the AR group, hematoxylin and eosin staining showed disordered arrangement of the nasal mucosa epithelium, cell shedding, eosinophilic infiltration, swelling of the glands, and submucosal vascular congestion. UA group showed reduced eosinophilic infiltration and orderly arrangement of the mucosal epithelium when compared with the ARE group. Immunohistochemical results showed that the expression of Eotaxin in the UA group was lower than that in the ARE group.. UA could relieve nasal symptoms caused by PM2.5 exposure, the possible mechanism of which is to inhibit the expression of Th2 cytokines, eosinophilic infiltration, and specific IgE production.

Topics: Animals; Cytokines; Disease Models, Animal; Female; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Particulate Matter; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Th2 Cells; Triterpenes; Ursolic Acid

Neutrophils are important phagocytic cells for host defense against pathogens. They are rapidly recruited to the site of infection, release antimicrobial peptides and cytokines, and engulf and kill microbes. Neutrophils also accumulate in allergic inflammatory sites. Here we characterized neutrophil accumulation in the nasal mucosa using a mouse model of allergic rhinitis, in which mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and then challenged by intranasal administration of OVA or PBS. In the nasal mucosa of both PBS- and OVA-challenged mice, we found a cell subset expressing the eosinophil marker Siglec-F in the Ly-6G

Topics: Animals; Antigens, Differentiation, Myelomonocytic; Cells, Cultured; Disease Models, Animal; Female; Mice; Mice, Inbred C57BL; Nasal Mucosa; Neutrophil Activation; Neutrophils; Ovalbumin; Phagocytosis; Rhinitis, Allergic; Sialic Acid Binding Immunoglobulin-like Lectins

This study was conducted to investigate the changes of serum interleukin-4 (IL-4), interferon-γ (IFN-γ), interleukin-17 (IL-17) and interleukin-10 (IL-10) in allergic rhinitis model rats after using the traditional Chinese nose sensitive pill (NSP) and its possible mechanism to treat allergic rhinitis. Forty Sprague Dawley (SD) rats were randomly divided into 4 groups of 10 rats each i.e. blank control group, model group, nose sensitive pill group and loratadine group. Allergic rhinitis was induced in all three groups (except blank control group) using ovalbumin as allergen. After successful induction of allergic rhinitis, intragastric administration of 0.9% NaCl solution, NSP or loratadine solution was carried-out, respectively. The behavior of rats was observed before administration and then after 1, 3 and 5 weeks. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of 4 cytokines in each group after 5 weeks. After 5 weeks study period, nasal symptoms of NSP group and loratadine group were significantly (P<0.01) lower than those of model group. Compared with blank control group, levels of IL-4 and IL-17 in model group increased, and levels of IFN-γ and IL-10 decreased significantly (P<0.01). Compared with model group, levels of IFN-γ and IL-10 increased but levels of IL-4 and IL-17 decreased significantly (P<0.01) in NSP and loratadine group. On the basis of findings of this study, NSP is an effective prescription to treat allergic rhinitis. One of its therapeutic mechanisms is to regulate balance between Th1/Th2 and Th17/Treg cells by influencing the levels of IL-4, IFN-γ, IL-17 and IL-10.

Topics: Animals; Disease Models, Animal; Drugs, Chinese Herbal; Female; Interferon-gamma; Interleukin-4; Nasal Mucosa; Ovalbumin; Random Allocation; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic

Th2 immune cells infiltration into nasal mucosa is one of the characters of allergic rhinitis (AR). We aimed to explore whether inhibition of Th2 immune cells infiltration would attenuate AR progression. AR mouse model was established by i.p. injection of ovalbumin (OVA). The infiltrated immune cells into nasal lavage fluid were detected by flow cytometry. Cytokine concentration in serum was determined by ELISA. AR mice symptoms were indicated by the number of sneezing and nasal rubbing events. In AR mice, CCL2 expression levels and CD45

Topics: Animals; Chemokine CCL2; Disease Models, Animal; Mice; Mice, Inbred BALB C; Monocytes; Nanomedicine; Nanoparticles; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; RNA, Small Interfering; Sneezing; Th2 Cells

The purpose of this study was the combination of curcumin and ovalbumin in free form or encapsulated into PLGA NPs (polylactic co-glycolic acid nanoparticles) to enhance their sublingual immunotherapy (SLIT) efficiency in mouse model of rhinitis allergic. PLGA NPs containing curcumin (CUR), ovalbumin (OVA) or both were prepared by emulsion-solvent evaporation method and characterized. After sensitization of BALB/C mice with ovalbumin, SLIT with free or encapsulated formulations was carried out and immunological profiles were evaluated. SLIT treatment with all synthesized PLGA formulations lead to significantly decreased total IgE. The combination immunotherapy in the present of free form of curcumin or ovalbumin with encapsulated forms of the another substance (P.OVA-CUR 10 and P.CUR 5-OVA), showed the highest level of IFN-γ:IL-4 compared to other target groups. On the other hands, a significant increasment was observed in this ratio between these optimal groups and treated group with subcutaneous administration of OVA as the most commonly used method for immunotherapy. The study of nasal lavage fluid (NALF) showed significant decreased levels of total and eosinophil cell count in the traeted nano-formulation groups. The histopathological results of NAL were also like normal with no cellular infiltration and no inflammation in the optimal formulations. Therefore, using curcumin and nanoparticles with allergen can be considerd as potential immune modulatory agents.

Topics: Allergens; Animals; Curcumin; Drug Delivery Systems; Female; Immunoglobulin E; Immunomodulation; Interferon-gamma; Interleukin-4; Mice, Inbred BALB C; Nanoparticles; Ovalbumin; Polylactic Acid-Polyglycolic Acid Copolymer; Rhinitis, Allergic; Spleen; Sublingual Immunotherapy

The study was aimed to investigate the protective effect of Asarum sieboldii Miq. essential oil (AEO) on ovalbumin (OVA)-induced allergic rhinitis (AR) in rats.. Sixty Sprague-Dawley male rats were randomly divided into six groups (n=10): control, model, cetirizine (Cet, 4.65 g/kg), and AEO (0.5, 1.5, 3 g/kg) groups. All animals except the control group received repeated intranasal instillation with 20 μl of 20% OVA in Al(OH)3 saline solvent for 15 days. The control group was intranasally instilled with 5 mg/ml of Al(OH)3 instead of the same procedure. In the 15 days, Cet and AEO were orally administrated for 28 days. At the end of the drug administration, 20 μl of 5% OVA was given to animals to stimulate allergic reaction, then the rat behavioral detection, assessment of the patho-morphological changes in nasal mucosa, and the serum biomarkers were determined. The result showed that AEO could significantly reduce the amount of nasal secretions, sneezing, and the degree of nasal scratching in AR rats with EC50 = 1.5 and 2.8 g/kg, respectively. The degree of nasal mucosal inflammation in AEO group improved, the levels of immunoglobulin E (IgE), histamine, IL-4, IL-5, IL-17 were decreased, and the level of IFN-γ was increased obviously with EC50 = 2 g/kg.. The study suggested that the possible mechanism might be related with the inhibition of histamine release and regulation of the cytokine levels, which plays an important role in the treatment of AR.

Topics: Animals; Anti-Allergic Agents; Asarum; Behavior, Animal; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Histamine; Immunoglobulin E; Male; Nasal Mucosa; Oils, Volatile; Ovalbumin; Plant Oils; Rats, Sprague-Dawley; Rhinitis, Allergic

Mangiferin (MF), extracted from mango trees, is considered to have anti-inflammatory, anti-apoptotic, and antioxidant effects. However, its effects on allergic rhinitis (AR), remain unclear. We investigated the mechanisms underlying the protective action of MF in ovalbumin (OVA)-induced AR models. AR was induced by OVA challenge in BALB/c mice. Prior to this, MF and dexamethasone were administered. Mice were examined for nasal mucosal inflammation, the generation of allergen-specific cytokine response, and histopathological changes in the nasal mucosa and lung tissue. MF ameliorated nasal symptoms and nasal mucosa inflammation in OVA-induced AR and reduced inflammatory cell infiltration and epithelial disruption in these tissues. MF inhibited the overproduction of Th2/Th17 cytokines and transcription factors. MF downregulated the HO-1/Nrf2 pathways, reduced oxidative stress biomarker levels, and the NF-κB signaling pathways were inhibited. MF exerts protective effects in AR by inhibiting NF-κB and activating HO-1/Nrf2 pathways. MF could be used for the treatment of AR.

Topics: Animals; Cytokines; Heme Oxygenase-1; Inflammation; Male; Mice, Inbred BALB C; Nasal Mucosa; NF-E2-Related Factor 2; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Signal Transduction; Th17 Cells; Th2 Cells; Xanthones

CARAS is an airway inflammation of allergic individuals, with a type 2 immune response. The pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study evaluated the alkaloids warifteine (War) and methylwarifteine (Mwar) from Cissampelos sympodialis in CARAS experimental model. Therefore, BALB/c mice were ovalbumin (OVA) sensitized and challenged and treated with both alkaloids. Treated animals showed a decrease (p < 0.05) of allergic signs as sneezing and nasal rubbings, histamine nasal hyperreactivity, and inflammatory cell migration into the nasal (NALF) and the bronchoalveolar (BALF) fluids, main eosinophils. In the systemic context, only Mwar reduced eosinophilia, however, both alkaloids reduced the serum levels of OVA-specific IgE. Histological analysis revealed that the alkaloids decreased the inflammatory cells into the subepithelial and perivascular regions of nasal tissue and the peribronchiolar and perivascular regions of lung tissue. Hyperplasia/hypertrophy of nasal and lung goblet cells were reduced in alkaloid treated animals; however, the treatment did not change the number of mast cells. The lung hyperactivity was attenuated by reducing hyperplasia of fibroblast and collagen fiber deposition and hypertrophy of the lung smooth muscle layer. The immunomodulatory effect was by decreasing of type 2 and 3 cytokines (IL-4/IL-13/IL-5 and IL-17A) dependent by the increasing of type 1 cytokine (IFN-γ) into the BALF of treated sick animals. Indeed, both alkaloids reduced the NF-кB (p65) activation on granulocytes and lymphocytes, indicating that the alkaloids shut down the intracellular transduction signals underlie the transcription of T

Topics: Alkaloids; Animals; Anti-Allergic Agents; Asthma; Behavior, Animal; Bronchoalveolar Lavage Fluid; Cissampelos; Collagen; Cytokines; Disease Models, Animal; Eosinophils; Female; Immunoglobulin E; Inflammation; Lung; Mast Cells; Mice, Inbred BALB C; Mucus; Nasal Lavage Fluid; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Signal Transduction; Sneezing; Transcription Factor RelA

The efficacy improvement of current sublingual immunotherapy (SLIT) for preventing and treating respiratory airway allergic diseases is the main purpose of many investigations. In this study, we aimed to assess whether ovalbumin (Ova) encapsulated poly (lactic-co-glycolic) acid nanoparticles (PLGA NPs) decorated with dendritic cells (DCs)-specific aptamer could be applied for this purpose.The nanoparticles containing Ova were synthesized by emulsion/solvent evaporation method and attached to DCs-specific aptamer. Ova-sensitized BALB/c mice have been treated in five ways: subcutaneously with free Ova (SCIT), sublingually either with free Ova, Ova-PLGA NPs (two doses), Apt-Ova-PLGA NPs (two doses) and placebo/control Apt-Ova-PLGA NPs. For assessment of immunologic responses, IL-4, IFN-γ, IL-17, IL10, and TGF-β and IgE antibody levels were measured by ELISA and T cell proliferation were evaluated by MTT. In addition, lung and nasal histological examinations, NALF cells counting were carried out. Results declared that the lowest IgE and IL- 4 levels were observed in Apt-Ova-PLGA NPs (both doses). In the other hands, Apt-Ova-PLGA NPs (high dose) showed the highest increase of IFN- γ and TGF- β, decrease of IL-17 levels, total cell count and T-cell proliferation. IL-10 levels showed more decrease in SCIT, Apt-Ova-PLGA NPs (high dose) and Ova-PLGA NPs (high dose) than other groups. Histopathological examinations also confirmed in vitro results. Our findings suggest SLIT with this functionalized delivery system could be a promising approach for promoting the SLIT efficiency by decreasing the required allergen doses through specific delivery of allergen to sublingual DCs and enhancing the suppression of allergic responses.

Topics: Allergens; Animals; Aptamers, Nucleotide; Dendritic Cells; Female; Mice, Inbred BALB C; Nanoparticles; Ovalbumin; Polylactic Acid-Polyglycolic Acid Copolymer; Rhinitis, Allergic; Sublingual Immunotherapy

Allergic rhinitis is the most prevalent atopic disorder worldwide. Inflammation is believed to participate in allergic rhinitis. Previous studies indicate that hypoxia-inducible factor (HIF) promotes the development of allergic rhinitis, and dendritic cells are also involved in allergic rhinitis.. We explored the consequences of HIF1α deficiency in dendritic cells on allergic rhinitis. Allergic rhinitis in mice was induced by ovalbumin (OVA). The levels of IgE, leukotriene C4 (LTC4), eosinophil cationic protein (ECP), prostaglandin D2 (PGD2), IFN-γ, IL-2, IL-4, IL-5, IL-10, and IL-13 in serum or nasal lavage fluid (NLF) were detected by ELISA. Inflammatory cells in NLF were counted by hemocytometer. The protein levels of p-ERK1/2, p-p38, p-JNK2, SIRT1, p-IκBα, and p65 were determined by Western blot.. HIF1α deficiency in dendritic cells (HIF1αCD11c-/-) decreased sneezing and nasal rubbing, the production of OVA-specific IgE, LTC4, and ECP in serum and NLF, and the numbers of leukocytes, eosinophils, lymphocytes, and neutrophils in NLF. Th1 cytokines increased, while Th2 cytokines decreased in HIF1aCD11c-/- mice. SIRT1/NF-κB signaling was inhibited in HIF1αCD11c-/- mice, while SIRT1 inhibitor administration in HIF1αCD11c-/- mice attenuated the symptoms and inflammatory indicators of allergic rhinitis.. HIF1α deficiency in dendritic cells attenuates symptoms and inflammatory indicators of allergic rhinitis in a SIRT1-dependent manner.

Topics: Allergens; Animals; Dendritic Cells; Disease Models, Animal; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Signal Transduction; Sirtuin 1

Allergic rhinitis (AR) is a common chronic condition characterized by inflammation of the nasal mucosa. The correlation of microRNAs (miRNAs) in AR has been highlighted particularly due to their roles in regulating inflammatory responses. The aim of this study was to explore the anti-inflammatory mechanism by which miR-345-5p regulates the toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway in mice with AR. Initially, the putative miR-345-5p binding sites on the 3'untranslated region of TLR4 was predicted and verified. AR models were established using ovalbumin, after which the functional role of miR-345-5p in AR was determined using gain- and loss-of-function approaches. We found that miR-345-5p was poorly expressed in nasal mucosal tissues of mice with AR. Meanwhile, TLR4 expression and the TLR4/NF-κB pathway were identified to be promoted, which were then suppressed in the presence of overexpressed miR-345-5p. In addition, nasal epithelial cell apoptosis and fibrosis were inhibited in response to miR-345-5p overexpression and TLR4 silencing. Furthermore, miR-345-5p overexpression and TLR4 silencing were observed to decrease Th2 cells, expression of pro-inflammatory factors, but to increase Th1 cells and expression of anti-inflammatory factors. This study demonstrates an important role of miR-345-5p in alleviating the inflammatory response in mice with AR by inhibiting the TLR4/NF-κB pathway. Therefore, a better understanding of this process may aid in the development of novel therapeutic agents of AR.

Topics: 3' Untranslated Regions; Animals; Anti-Inflammatory Agents; Apoptosis; Disease Models, Animal; Epithelial Cells; Female; Fibrosis; Inflammation; Mice, Inbred BALB C; MicroRNAs; Myeloid Differentiation Factor 88; Nasal Mucosa; NF-kappa B p50 Subunit; Ovalbumin; Receptors, Interleukin; Rhinitis, Allergic; Signal Transduction; Toll-Like Receptor 4

BACKGROUND Allergic rhinitis (AR) is a prevalent atopic disorder caused by immune imbalance. Chlorogenic acid (CGA) has antibacterial, antiviral, antioxidative and immunoregulatory effects, but its role in anaphylactic disease remains unclear. The current study aimed to investigate the function of CGA in AR. MATERIAL AND METHODS AR mice models were induced with ovalbumin (OVA) by orally administrating the mice with 50 mg/kg (L-CGA), 100 mg/kg (M-CGA), or 200 mg/kg (H-CGA) of CGA. The number of nasal rubbings and sneezes was recorded. Afterward, the mice were sacrificed for the collection of blood, nasal lavage fluid (NALF), and nasal tissues. The cells in NALF were counted by hemocytometer and stained by Diff-Quick. Nasal mucosa was observed by H&E staining. ELISA testing was conducted for detecting the levels of anti-OVA antibodies and Th1/Th2-related cytokine. Quantitative real-time polymerase chain reaction experiments were conducted to determine mRNA expressions of Th1/Th2-related cytokines. RESULTS In the OVA-induced AR mice, CGA treatment reduced nasal rubbing and sneezing, and also suppressed the number of total cells, eosinophils, neutrophils, lymphocytes, macrophages, and epithelial cells in NALF. OVA-induced up-regulation of nasal mucosa thickness was inhibited by CGA, and the effects of OVA on IgE, IgG1, and IgG2a were reversed by CGA. The regulatory effects of OVA on mRNA expressions and levels of Th1/Th2-related cytokines were abolished by CGA treatment in AR mice. CONCLUSIONS CGA can alleviate allergic inflammatory responses through regulating Th1/Th2 balance in OVA-induced allergic rhinitis mice.

Topics: Animals; Chlorogenic Acid; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Eosinophils; Inflammation Mediators; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Real-Time Polymerase Chain Reaction; Rhinitis, Allergic; Th1-Th2 Balance

Allergic rhinitis (AR) is a common chronic inflammatory disease of the upper respiratory tract. Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and belongs to environmental endocrine disruptors (EDCs). It can be entered the human body which is harmful to health. The relationship between DEHP and AR is still inconclusive. This study aims to investigate the effect of environmental pollutants DEHP on AR. By examining DEHP metabolites in the urine of AR patients and building an AR model. 24 BALB/c mice were used as the study subjects, and ovalbumin (OVA) and DEHP (3 mg/kg/body) were used for intragastric administration. They were divided into control group, DEHP group, OVA group and OVA + DEHP group. Examination, behavioral scoring, inflammatory factor testing, oxidative stress testing, detection of aryl hydrocarbon receptor (AhR) and signaling pathways CYP1A1 and CYP1B1 related proteins and mRNA. The concentrations of 3 metabolites of DEHP (MEHHP, MEOHP, and MEHP) in urine of AR patients were higher. And HE-staining showed that for the control group, many chronic inflammatory cell infiltration and nasal mucosal destruction were observed in the OVA + DEHP group and were more severe than the OVA group. Allergic symptom scores were obtained from sneezing, scratching, number of scratching, and nose flow. The scores of the OVA group and the OVA + DEHP group were higher than 7 points. Serum ELISA and nasal mucosal oxidative stress tests are more serious in the OVA + DEHP group. The expression of AhR protein and its mRNA was increased in the DEHP group, OVA group and OVA + DEHP group. The OVA + DEHP group was more significant in the OVA group and DEHP group. And the mRNAs of the AhR-related signaling pathways CYP1A1 and CYP1B1 were also more prominent in the OVA + DEHP group. DEHP may aggravate its inflammatory response through the AhR pathway closely related to the environment. When combined with OVA, DEHP can further aggravate the OVA-induced nasal inflammatory response and make the nasal cavity have undergone severe changes, and many inflammatory cells have infiltrated. DEHP has shown an adjuvant effect, and the AhR-related signaling pathways CYP1A1 and CYP1B1 may be critical.

Topics: Animals; Cytochrome P-450 CYP1A1; Diethylhexyl Phthalate; Disease Models, Animal; Environmental Exposure; Environmental Pollutants; Inflammation; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Oxidative Stress; Rhinitis, Allergic

Topics: Animals; Anti-Inflammatory Agents; Asthma; beta-N-Acetylhexosaminidases; Body Weight; Bronchi; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Capsaicin; Cordyceps; Cytokines; Disease Models, Animal; Eosinophil Peroxidase; Female; Histamine Release; Immunization; Immunoglobulin E; Mast Cells; Methacholine Chloride; Mice, Inbred BALB C; Mycelium; Nasal Lavage; Ovalbumin; Rats, Sprague-Dawley; Rhinitis, Allergic; Skin; Spleen; Trachea

Bisphenol A (BPA) is found in many plastic products and is thus a common environmental endocrine disruptor. Plastic-related health problems, including allergic diseases, are attracting increasing attention. However, few experimental studies have explored the effect of BPA on allergic rhinitis (AR). We explore whether BPA was directly related to the allergic inflammation induced by ovalbumin (OVA) in AR mice.. We first constructed OVA-induced mouse model, and after BPA administration, we evaluated nasal symptoms and measured the serum OVA-specific IgE levels by ELISA. Th2 and Treg-related cytokines of nasal mucosa were measured by cytometric bead array. Th2 and Treg-specific transcription factor levels were assayed by PCR. The proportions of CD3. Compared to OVA-only-induced mice, BPA addition increased nasal symptoms and serum OVA-specific IgE levels. OVA and BPA coexposure significantly increased IL-4 and IL-13 protein levels compared to those after OVA exposure alone. BPA plus OVA tended to decrease the IL-10 protein levels compared to those after OVA alone. Coexposure to OVA and BPA significantly increased the GATA-3-encoding mRNA level, and decreased the levels of mRNAs encoding Foxp3 and Helios, compared to those after OVA exposure alone. BPA increased the Th2 cell proportion, and decreased that of Tregs, compared to the levels with OVA alone.. BPA exerted negative effects by exacerbating AR allergic symptoms, increasing serum OVA-specific IgE levels, and compromising Th2 and Treg responses.

Topics: Air Pollutants, Occupational; Allergens; Animals; Benzhydryl Compounds; Cytokines; Disease Models, Animal; Disease Susceptibility; Female; Immunoglobulin E; Inflammation Mediators; Mice; Mucous Membrane; Ovalbumin; Phenols; Rhinitis, Allergic; T-Lymphocyte Subsets; Transcription Factors

Allergic rhinitis (AR) is a non-infectious chronic inflammatory disease of nasal mucosa provoking T helper cell (Th) 17 response. Chlorogenic acid (CGA), one of the most abundant polyphenol compounds in various agricultural products, possesses antiviral, anti-inflammatory, and antibacterial properties. However, the effect of CGA on AR is unclear. Thus, our study explored the effect of CGA in modulating AR-related symptoms and immunoreaction, especially Th17 response. AR mice were induced by ovalbumin (OVA) administration and further treated with CGA or dexamethasone (Dex). The frequencies of rubbing and sneezing of AR mice were recorded. Histopathological analysis of nasal mucosa was conducted by Hematoxylin-Eosin and Periodic acid-Schiff stainings. The serum and nasal mucosa levels of OVA-immunoglobulin (Ig)E, interferon (IFN)-γ, retinoic acid-associated nuclear orphan receptor (ROR)-γt, and interleukin (IL)-17A were measured by enzyme-linked immunosorbent assay, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), or Western blot. The ratio of CD4+IL-17+Th17 cells to CD4+ T cells in peripheral blood of AR mice was assessed by flow cytometer. CGA diminished the frequencies of rubbing and sneezing of AR mice in a concentration-dependent manner. CGA attenuated histopathological abnormalities and decreased goblet cell number in nasal mucosa of AR mice. CGA decreased the serum levels of OVA-IgE, ROR-γt, and IL-17A, while increasing the serum level of IFN-γ in AR mice. Meanwhile, CGA decreased the ratio of CD4+IL-17+Th17 cells to CD4+T cells in peripheral blood and the mRNA and protein levels of IL-17A and ROR-γt in AR mice. CGA ameliorated AR-related symptoms in mice by regulating Th17 cells, which could be a candidate for the treatment of AR.

Topics: Animals; Anti-Allergic Agents; Cell Differentiation; Chlorogenic Acid; Dexamethasone; Disease Models, Animal; Glucocorticoids; Goblet Cells; Immunoglobulin E; Interferon-gamma; Interleukin-17; Mice, Inbred BALB C; Nasal Mucosa; Nuclear Receptor Subfamily 1, Group F, Member 3; Ovalbumin; Rhinitis, Allergic; Th17 Cells

Topics: Animals; Chamaecyparis; Disease Models, Animal; Female; Immunoglobulin E; Immunologic Factors; Inflammation Mediators; Mice, Inbred BALB C; Nasal Lavage Fluid; Nasal Mucosa; Oils, Volatile; Ovalbumin; Rhinitis, Allergic; Spleen; Transcription Factors

The host-microbial commensalism can shape the innate immune responses in respiratory mucosa and nasal microbiome also modulates front-line immune mechanism in the nasal mucosa. Inhaled allergens encounter the host immune system first in the nasal mucosa, and microbial characteristics of nasal mucus directly impact the mechanisms of initial allergic responses in nasal epithelium. However, the roles of the nasal microbiome in allergic nasal mucosa remain uncertain. We sought to determine the distribution of nasal microbiomes in allergic nasal mucosa and elucidate the interplay between nasal microbiome Staphylococcus species and Th2 cytokines in allergic rhinitis (AR) models.. Staphylococcus aureus (AR-SA) and S. epidermidis (AR-SE) were isolated from the nasal mucosa of patients with AR. The influence of nasal microbiome Staphylococcus species on allergic nasal mucosa was also tested with in vitro and in vivo AR models. Pyrosequencing data showed that colonization by S. epidermidis and S. aureus was more dominant in nasal mucus of AR subjects. The mRNA and protein levels of IL-33 and TSLP were significantly higher in AR nasal epithelial (ARNE) cells which were cultured from nasal mucosa of AR subjects, and exposure of ARNE cells to AR-SA reduced IL-33 mRNA and secreted protein levels. Particularly, ovalbumin-driven AR mice inoculated with AR-SA by intranasal delivery exhibited significantly reduced IL-33 in their nasal mucosa. In the context of these results, allergic symptoms and Th2 cytokine levels were significantly downregulated after intranasal inoculation of AR-SA in vivo AR mice.. Colonization by Staphylococcus species was more dominant in allergic nasal mucosa, and nasal commensal S. aureus from subjects with AR mediates anti-allergic effects by modulating IL-33-dependent Th2 inflammation. The results demonstrate the role of host-bacterial commensalism in shaping human allergic inflammation.

Topics: Animals; Corynebacterium; Cytokines; Disease Models, Animal; Enterobacter aerogenes; Epithelial Cells; Female; Gene Expression; Humans; Immunity, Innate; Interleukin-33; Mice, Inbred BALB C; Micrococcus luteus; Mucus; Nasal Mucosa; Ovalbumin; Primary Cell Culture; Rhinitis, Allergic; RNA, Messenger; Staphylococcus aureus; Staphylococcus epidermidis; Symbiosis

The aim of this study was to analyze the 4-carvomenthenol (carvo) oral treatment on the experimental model of the combined allergic rhinitis and asthma syndrome (CARAS). BALB/c mice were OVA-sensitized on day zero and 7th (50 μg/mL OVA in 10 mg/mL Al (OH)3) and OVA-challenged (5 mg/mL, 20 μL/animal) for three weeks. In the last week, the animals were dally challenged with aerosol of OVA and the carvo treatment (12.5, 25 or 50 mg/kg) occurred one hour before each OVA-challenge. Data were analyzed and p < 0.05 was considered significant. Carvo (12.5-50 mg/kg) decreased significantly the eosinophil migration into the nasal (NALF) and bronchoalveolar (BALF) cavities as well as on the nasal and lung tissues of sick animals. The treatment also decreased mucus production on both tissue sections stained with PAS (periodic acid-Schiff satin). In addition, the histological analyzes demonstrated that sick mice presented hyperplasia and hypertrophy of the lung smooth muscle layer followed by increasing of extracellular matrix and carvo (50 mg/kg) inhibited these asthmatic parameters. We analyzed the allergic rhinitis signals as nasal frictions and sneezing and observed that carvo decreased these two signals as well as serum OVA-specific IgE titer, type 2 cytokine synthesis, mainly IL-13, with increasing of IL-10 production. Decreasing of IL-13 production corroborated with decreasing of mucus production and these effects were dependent on p38MAPK/NF-κB(p65) signaling pathway inhibition. Therefore, these data demonstrated that a monoterpene of essential oils presents anti-allergic property on an experimental model of CARAS suggesting a new drug prototype to treat this allergic syndrome.

Topics: Allergens; Animals; Anti-Allergic Agents; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Female; Interleukin-13; Lung; Menthol; Mice, Inbred BALB C; Mucus; NF-kappa B; Ovalbumin; p38 Mitogen-Activated Protein Kinases; Rhinitis, Allergic; Signal Transduction; Syndrome

Allergic rhinitis (AR) is nasal inflammation caused by allergy and the prevalence of AR is rising globally. In this investigation, we used ovalbumin-provoked AR to examine the antiallergic, anti-inflammation activities of mangiferin. Mangiferin is a xanthone found in higher plants as well as mango and it has numerous health benefits including antitumor, antioxidant, antimutagenic, antidiabetic, antibacterial, and anti-inflammatory properties. Alternatively, the antiallergic action of mangiferin on AR has been not yet investigated. Mangiferin administration reduced the symptoms of nasal allergy such as sneezing as well as rubbing in AR. Besides, the generated MDA through allergen administration was considerably diminished as a result of mangiferin treatment. Additionally, mangiferin prevented the STAT3 as well as NF-κBp65 signaling pathway activation in the cytosol, which resulted in the anti-inflammatory cytokines being upregulated, whereas, the pro-inflammatory cytokines were downregulated. Moreover, mangiferin reduced signs of ciliary loss, vascular congestion in the lamina, goblet cell elevation, and eosinophil filtration in the AR model. Hence, our findings suggest that mangiferin is a promising approach for immunotherapy in AR disease.

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Interleukin-6; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Signal Transduction; STAT3 Transcription Factor; Transcription Factor RelA; Xanthones

Madi-Ryuk (MDR) is a traditional Korean medicine and it has been widely used in Korea to treat arthritis and we previously reported the anti-allergic inflammatory effect of MDR in vitro model. However, therapeutic evidence of MDR on in vivo model of allergic inflammatory reaction has not yet been demonstrated. The research purpose was to investigate the efficacy of MDR and its active ingredient tannic acid (TA) in ovalbumin (OVA)-induced AR mice model. OVA-challenged AR mice orally medicated MDR or its active ingredient TA daily for ten days. In mice having a AR, MDR and TA prominently diminished number of rubs and levels of histamine, IgE, thymic stromal lymphopoietin, interleukin (IL)-1β, IL-4, IL-5, IL-13, IL-33, and tumor necrosis factor-α. In addition, protein expression levels and activities of caspase-1 were declined by oral medication of MDR and TA. Decline in levels of macrophage inflammatory protein-2 and intercellular adhesion molecules-1 and reduction in penetrations of inflammatory cells into inflamed tissue were also noted in MDR and TA groups. Taken together, identification of MDR effect in preclinical models suggests that MDR may be a therapeutic drug for the treatment and prevention of AR.

Topics: Animals; Anti-Inflammatory Agents; Caspase 1; Chemokine CXCL2; Cytokines; Disease Models, Animal; Eosinophils; Histamine; Immunoglobulin E; Inflammation; Interleukin-1beta; Medicine, Korean Traditional; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Tannins; Thymic Stromal Lymphopoietin; Tumor Necrosis Factor-alpha

Allergic rhinitis is a chronic inflammatory disease of the upper respiratory tract, which is associated with high incidence of anxiety symptom. There is evidence that medial prefrontal cortex modulates anxiety-related behaviors and receives projections from olfactory bulb. Since olfactory dysfunction has been reported in allergic rhinitis, we aimed to evaluate anxiety-like behavior and oscillations of olfactory bulb-medial prefrontal cortex circuit in an animal model of allergic rhinitis. The number of open arm entries in elevated zero maze was significantly reduced in sensitized rats exposed to intranasal ovalbumin compared to the control group, which was indicating the enhancement of anxiety-like behavior in allergic rhinitis animals. Analysis of local field potentials in olfactory bulb and medial prefrontal cortex during immobility and exploration state showed that anxiety-like behavior induced by allergic rhinitis was in association with increased activity of medial prefrontal cortex and enhancement of olfactory bulb-medial prefrontal cortex coupling in delta and theta bands. Moreover, in allergic rhinitis animals, theta strongly coordinates local gamma activity in olfactory bulb and medial prefrontal cortex, which means to have a strong local theta/gamma coupling. We suggested that disruption of olfactory bulb-medial prefrontal cortex circuit due to allergic reactions might have a governing role for inducing anxiety-like behavior in the allergic rhinitis experimental model.

Topics: Action Potentials; Animals; Anxiety; Behavior, Animal; Connectome; Disease Models, Animal; Male; Olfactory Bulb; Ovalbumin; Prefrontal Cortex; Rats; Rhinitis, Allergic; Specific Pathogen-Free Organisms

Allergic rhinitis is a global cause of disability, characterized by airway inflammation. Sumatriptan is a 5-hydroxytryptamine 1B/1D (5HT1B/1D) agonist used as a treatment for migraine headaches. Activation of 5HT1B/1D receptors can inhibit the release of neuropeptides and inhibit the inflammation cascades. This study investigated the effect of sumatriptan on ovalbumin-induced allergic rhinitis model in mice and the role of nitric oxide.. Female Balb/c mice were sensitized by intraperitoneal ovalbumin and challenged by intranasal ovalbumin. Mice received sumatriptan in doses 3, 10, 30 μg/kg intraperitoneally, 30 min before the last ovalbumin challenge.. Intraperitoneal injection of sumatriptan significantly decreased the nasal scratching, IL-4 and serum IgE levels of allergic mice, but it increased IFNγ levels. Histopathological analysis showed that the number of eosinophils was significantly elevated in nasal mucosa of ovalbumin-induced allergic mice, while sumatriptan treatment significantly reduced the number of eosinophils. GR-127935, a selective 5-HT1B/1D-receptor antagonist, reversed the anti-allergic effects of sumatriptan. Acute administration of l-NAME, a non-specific inhibitor of nitric oxide synthase, along with sumatriptan attenuated the anti-allergic effects of sumatriptan but chronic administration of l-NAME did not affect the influences of sumatriptan. Furthermore, sumatriptan decreased the inducible nitric oxide synthase (iNOS) protein expression in allergic mice, but it did not change the concentration of eNOS protein.. This study shows that sumatriptan administration is associated with anti-allergic effects which are through 5HT1B/1D receptors. Decrease in iNOS expression and changes in T-helper 1&2 cytokines levels may indicate the involvement of inducible NOS and inflammation.

Topics: Animals; Disease Models, Animal; Female; Mice; Mice, Inbred BALB C; Nitric Oxide; Nitric Oxide Synthase Type II; Ovalbumin; Rhinitis, Allergic; Serotonin 5-HT1 Receptor Agonists; Signal Transduction; Sumatriptan

To investigate the protective effect of excretory-secretory protein (AES) from adult. Eighteen female BALB/c mice were randomly divided into three groups, including the blank control group (Group A), OVA-induced rhinitis group (Group B) and AES treatment group (Group C). Mice in Group A were given PBS. Mice in Group B were intraperitoneally injected with antigen adjuvant suspension for systemic sensitization, once every other day for seven times; then, local excitation was intranasally induced with 5% OVA solution once a day for seven times to establish a mouse model of allergic rhinitis. In addition to induction of allergic rhinitis, mice in Group C were given 25 μg AES at baseline sensitization and local excitation. Following the final challenge, mice were observed for 30 min in each group, and the behavioral score was evaluated. The serum levels of IFN-γ, IL-4, IL-5, IL-10 and TGF-β were determined using an enzyme-linked immunosorbent assay in mice, and the pathological changes of mouse nasal mucosa were observed under a microscope.. There was a significant difference in the mouse behavioral scores among the three groups (

Topics: Animals; Antigens, Helminth; Disease Models, Animal; Female; Helminth Proteins; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Trichinella spiralis

The identification of new approaches and intervention targets for the treatment of AR is urgently needed. We aimed to investigate the effect of blocking the OX40/OX40L signaling pathway by small interfering RNA (siRNA) on ovalbumin (OVA)-induced AR in a mouse model.. After establishment of the AR model, the mice were interfered by siRNA-OX40L (experimental group), siRNA-C (negative control group), or PBS (control group). Nose scratching, sneezing and nasal discharge were observed. OX40L mRNA and protein and the IL-5, TNF-α, regulatory T cell (Treg) -specific marker Foxp3, and eosinophil (EOS) levels were analyzed.. The numbers of nose scratching and sneezing were significantly lower in the siRNA-OX40L-treated group (p <0.05). After the intervention of siRNA-OX40L, OX40L mRNA and protein levels were significantly inhibited (p <0.05), but the Foxp3 level was significantly increased in the experimental group (p <0.05). The IL-5 and TNF-α levels were significantly lower in the experimental group (p <0.05), and the reduction was more evident for the Th2-type cytokine IL-5 than for the Th1-type cytokine TNF-α. Few or no EOSs were found in the nasal mucosal epithelium of the experimental group (p <0.05), whereas EOS infiltration was significant in the other two groups.. Blockage of the OX40/OX40L signaling pathway with siRNA-OX40L interference can inhibit allergic reactions and relieve allergic symptoms in AR mice. The underlying mechanism may be related to correcting Th2 immune deviation, inducing immune tolerance, and promoting Treg production.

Topics: Animals; Disease Models, Animal; Mice; Ovalbumin; OX40 Ligand; Rhinitis, Allergic; RNA, Small Interfering; Signal Transduction

To investigate the effects of acupuncture with dexamethasone (A. Dex) on allergic rhinitis (AR) by injecting dexamethasone into the Zusanli (ST 36) acupoint.. Thirty 6-week-old female BALB/c mice were sensitized on days 1, 5, and 14 by intraperitoneal injection of 100 µg of ovalbumin (OVA). The mice were then randomly divided into six groups (n = 5 in each group). Five groups were sensitized intranasally with 2 μL of 1.5 mg of OVA for 10 consecutive days, while one group was sensitized intranasally with PBS in a similar manner as a negative control group. One hour before each administration of intranasal OVA, two groups were orally administered either a control vehicle (distilled water; AR control group) or 200 μg/kg Dex (O. Dex group), while three groups received A. Dex at Zusanli (ST 36) with Dex concentrations of 2, 20, and 200 μg/kg for each group, respectively. AR symptoms were evaluated by measuring the rubbing score, which comprised the number of nose, ear, and eye rubs that occurred in the initial 10 min after OVA intranasal provocation on the 10th day. We isolated spleen, serum, and nasal mucosal tissue after measuring the rubbing score. Spleen weight was measured using an electronic microbalance. The levels of IgE, thymic stromal lymphopoietin, tumor necro- sis factor-α, intercellular adhesion molecule-1, and macrophage-inflammatory protein-2 in serum or nasal mucosal tissue were measured using enzyme-linked immunosorbent assays. The serum histamine levels of OVA-sensitized AR mice were measured using O-phthaldialdehyde spectrofluorometry. Western blot analysis was performed on nasal mucosal tissue extracts.. A. Dex significantly reduced the rubbing score, spleen weight, serum IgE, and serum histamine in OVA-sensitized mice. A. Dex significantly decreased the serum levels of inflammatory cytokines (thymic stromal lymphopoietin and tumor ne- crosis factor-α) in OVA-sensitized mice. A. Dex sig-nificantly reduced the nasal mucosal levels of inflammatory markers (intercellular adhesion molecule-1andmacrophage-inflammatory protein-2) inAR mice. A. Dex effectively attenuated the expression of caspase-1 and receptorinteractingprotein-2 in nasal mucosal tissue.

Topics: Acupuncture; Acupuncture Points; Animals; Caspase 1; Cytokines; Dexamethasone; Female; Intercellular Adhesion Molecule-1; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Thymic Stromal Lymphopoietin; Tumor Necrosis Factor-alpha

Allergic rhinitis is a sensitivity to allergens that causes swelling or puffiness of the nasal airways. The occurrence of allergic rhinitis is mounting worldwide. We examined whether fucoxanthin restrains the development of allergic rhinitis provoked by ovalbumin (OVA). In this study, allergic rhinitis in male BALB/c mice was induced with OVA. The object was to evaluate the effect of fucoxanthin on consequently allergic mice. Allergic responses like rubbing and sneezing were scored to reveal the effect of fucoxanthin in the induced and treated groups. Mean histological scores demonstrated variation in and between OVA-induced and fucoxanthin-treated groups in terms of ciliary loss, eosinophil infiltration, and the like. Lipid profiling (malondialdehyde) confirmed the restraining effect of fucoxanthin on allergic rhinitis. The present study showed that cytokine production, the induction of cell survival molecule NF-κB p65, and subsequent prevention of IκBα phosphorylation are controlled by fucoxanthin, and that interleukins (IL-5, IL-6, and IL-12) support STAT-3 binding to key elements that control IL-17A expression. Additionally, the study showed that interleukin-induced NF-κB and IκBα directly regulate interleukins in collaboration with STAT-3 and related cytokines. Levels of IgE and histamine are the most frequent medications used to treat allergic rhinitis. Considering our findings, we concluded that fucoxanthin represses the development of allergic rhinitis induced by OVA and thus might be a positive drug for its management.

Topics: Animals; Cytokines; Disease Models, Animal; Interleukin-17; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Protective Agents; Rhinitis, Allergic; Signal Transduction; STAT3 Transcription Factor; Transcription Factor RelA; Xanthophylls

This study aimed to examine whether probiotics, which suppressed the differentiation of splenic T cells into type 2 helper T (Th2) cells and induced into regulatory T cells in vitro, alleviate allergic rhinitis (AR) and gut microbiota disturbance. We isolated Bifidobacterium longum IM55 and Lactobacillus plantarum IM76 from human faecal microbiota and kimchi, respectively, and examined their effects on ovalbumin (OVA)-induced AR and gut microbiota disturbance in mice. Treatment with IM55, IM76, or their probiotic mixture (PM) significantly reduced OVA-induced allergic nasal symptoms and blood immunoglobulin E (IgE) levels in mice. These also reduced OVA-induced interleukin (IL)-4 and IL-5 levels in nasal tissues and bronchoalveolar lavage fluid (BALF) but increased OVA-suppressed IL-10 levels. Treatment with IM55, IM76, or PM reduced OVA-induced increase in the populations of mast cells, eosinophils, and Th2 cells and increased OVA-suppressed population of regulatory T cells in the BALF. Treatment with IM55, IM76, or PM also inhibited OVA-induced expression of IL-5 in lung and colon tissues and restored OVA-disturbed composition of gut microbiota Proteobacteria, Bacteroidetes, and Actinobacteria. These results suggest that IM55 and IM67 can alleviate AR by restoring Th2/Treg imbalance and gut microbiota disturbance.

Topics: Animals; Bifidobacterium longum; Bronchoalveolar Lavage Fluid; Colon; Cytokines; Disease Models, Animal; Dysbiosis; Female; Humans; Immunoglobulin E; Lactobacillus plantarum; Mice, Inbred BALB C; Ovalbumin; Probiotics; Rhinitis, Allergic; Spleen; T-Lymphocytes, Regulatory; Th2 Cells

Allergic rhinitis is an immunoglobulin-E (Ig-E)-mediated response driven by type 2 helper T cells. Hesperidin and thymol are biological agents that possess antioxidant and anti-inflammatory characteristics. The purpose of this study was to investigate the effects of hesperidin and thymol in rats with ovalbumin-induced allergic rhinitis.. Thirty adult Sprague-Dawley rats were randomly assigned into five groups, each containing six animals. The first group constituted the negative control group, while the remaining groups were exposed to an ovalbumin-induced model of allergic rhinitis. In the provocation stage, 4 mL/kg saline was administered to the positive control group, 10 mg/kg desloratadine to the reference group, 100 mg/kg hesperidin to the hesperidin group, and 20 mg/kg thymol to the thymol group, all by gastric lavage for 7 days. Nasal symptoms were scored on day 22. Rats were then sacrificed, and intracardiac blood specimens were collected to measure plasma total Ig-E, IL-5, IL-13, total antioxidant capacity (TAC), and total oxidant status (TOS) levels. Nasal tissues were extracted for histopathological and immunochemical examination.. Nasal symptom scores were highest in the positive control group, while hesperidin and thymol ameliorated these symptoms to the same extent as desloratadine. Ig-E, IL-5, IL-13, and TOS levels increased, while TAC levels decreased significantly in the allergic rhinitis group compared to the other groups. Significant improvement in these parameters was observed in both the hesperidin and thymol groups. At histopathological and immunohistochemical examination of the nasal cavity, severe allergic inflammation and severe TNF-α expression was determined in rats from the allergic rhinitis group. Mild inflammatory changes and mild TNF-α expression were observed in all three treatment groups.. Both hesperidin and thymol were effective in suppressing allergic symptoms and inflammation in the treatment of allergic rhinitis.

Topics: Animals; Anti-Infective Agents; Antioxidants; Disease Models, Animal; Hesperidin; Immunoglobulin E; Inflammation; Interleukin-13; Interleukin-5; Nasal Cavity; Ovalbumin; Oxidants; Rats, Sprague-Dawley; Rhinitis, Allergic; Thymol; Tumor Necrosis Factor-alpha

Dryopteris crassirhizoma (DC) is used as a traditional herbal remedy to treat various diseases, the tapeworm infection, common cold, and cancer in Korea, Japan, and China. DC also has the antioxidant anti-inflammatory and antibacterial activities. However, the anti-allergic inflammatory effect of DC and some of its mechanisms in allergic rhinitis model are unknown well.. The purpose of this study is to investigate the anti-allergic inflammatory effect of DC on the allergic rhinitis model, mast cell activation and histamine release.. Allergic rhinitis was induced in BALB/c mice by sensitization and challenge with ovalbumin (OVA). Different concentration of DC and dexamethasone was administrated by oral gavage on 1 h before the OVA challenge. Mice of the control group were treated with saline only. Then mice were evaluated for the presence of nasal mucosa inflammation, the production of allergen-specific cytokine response and the histology of nasal mucosa.. DC significantly ameliorated the nasal symptoms and the inflammation of nasal mucosa. DC also reduced the infiltration of eosinophils and mast cells in these tissues and the release of histamine in blood. Meanwhile, DC evidently inhibited the overproduction of Th2 cytokines and increased the Th1 and Treg cytokines in nasal lavage fluid by OVA. DC also reduced the levels of OVA-specific IgE, IgG1 and IgG2a in blood.. This study suggests that DC has a significant anti-allergic inflammatory effect in the nasal cavity. DC may have the therapeutic effect of allergic rhinitis.

Topics: Allergens; Animals; Anti-Allergic Agents; Cytokines; Disease Models, Animal; Dryopteris; Ethanol; Immunoglobulin E; Immunoglobulin G; Male; Mast Cells; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Plant Extracts; Rhinitis, Allergic; Solvents; Th2 Cells

Dysregulation of the coagulation cascade and fibrinolysis system may play an etiologic role in many diseases. Allergic diseases such as bronchial asthma, atopic dermatitis, and conjunctivitis are also associated with fibrin accumulation caused by a change in hemostasis. However, only a few studies have dealt with the relationship between allergic rhinitis (AR) and the coagulation system.. We investigated the difference of coagulation and fibrinolysis cascade components between an AR mouse model and a control mice.. BALB/c mice were sensitized and challenged with ovalbumin. Multiple parameters of coagulation cascade and fibrinolysis system such as factors II, V, VII, X, and XIII; tissue-type plasminogen activator; urokinase-type plasminogen activator (u-PA); plasminogen activator inhibitor-1 (PAI-1); and fibrin were compared between the AR model group and the control group.. The symptom scores and eosinophil counts were higher in the AR group than in the control group ( P < .01). The mRNA expression level of u-PA ( P = .040) was significantly lower, and the expression levels of factor II ( P = .038) and factor X ( P = .036) were significantly higher, in the AR group. Immunohistochemical staining revealed that most of the fibrinolysis system and coagulation cascade components were localized to the epithelium, endothelium, and submucosal glands of the nasal mucosa. u-PA was downregulated in the AR group, whereas fibrin deposition was more prominent in the AR group than in the control group.. In AR, particular components of the coagulation cascade were increased and fibrinolysis system was decreased compared to normal control. This difference may be associated with the fibrin deposition in the mucosa of AR mouse model.

Topics: Animals; Blood Coagulation; Blood Coagulation Factors; Disease Models, Animal; Eosinophils; Female; Fibrin; Fibrinolysis; Leukocyte Count; Mice, Inbred BALB C; Nasal Lavage Fluid; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; RNA, Messenger

We previously reported that dendritic cells (DCs) transfected with CD40 siRNA and pulsed by ovalbumin (OVA) (CD40-silenced OVA DCs) inhibited allergic responses through facilitation of regulatory T cells (Tregs). However, to our knowledge, no prior study has examined allergen-specific therapy by administration of siRNA-induced Tregs for the control of allergy.. We aimed to investigate the effect of Tregs induced in vitro on allergic responses and symptoms in vivo.. Mice were treated with Tregs (OVA DCs-induced Tregs) induced by CD40-silenced OVA DCs or Tregs (nonantigen DCs-induced Tregs) induced by DCs transfected with CD40 siRNA and pulsed with no antigen, and the effects of these Tregs on allergic responses were estimated.. Administration of nonantigen DCs-induced Tregs prevented not only OVA-induced allergy but also keyhole limpet hemocyanin-induced allergy. Administration of OVA DCs-induced Tregs significantly reduced the number of sneezes and nasal rubbing movements, eosinophilia in the nasal mucosa, and the level of OVA-specific IgE in mice with OVA-induced allergy, compared with CD40-silenced nonantigen DC-induced Tregs in numbers 20 times greater, even in mice with established allergic rhinitis. Furthermore, Tregs induced by CD40-silneced DCs pulsed with Cry j 1, a major allergen of Japanese cedar pollen, inhibited Japanese cedar-induced allergy.. This study shows for the first time that both antigen-independent Tregs and antigen-specific Tregs can be induced by siRNA, and that therapy with siRNA-induced Tregs inhibits allergic responses and symptoms. It also shows that antigen-specific Tregs have more potent effects in inhibiting allergic responses than antigen-nonspecific Tregs.

Topics: Allergens; Animals; CD40 Antigens; Dendritic Cells; Desensitization, Immunologic; Immunoglobulin E; Male; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; T-Lymphocytes, Regulatory

Piper nigrum L. is commonly used as a traditional medicine and food in many countries. It has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the effect of P. nigrum on allergic rhinitis (AR) has been unclear. In the present study, an OVA-induced AR mice model were established to investigate the anti-allergic, anti-inflammation properties of P. nigrum fruit extract (PNE). Oral administrations of PNE inhibited the allergic nasal symptoms including rubbing and sneezing in the early-phage of AR. In both NALF and nasal tissue, PNE suppressed the inflammatory cells accumulation, specifically with eosinophils in NALF. Additionally, PNE prevented the activation of STAT3 and NFκBp65 signaling in the cytoplasm which led to increasing the synthesis of the anti-inflammatory Th1 cytokines and suppressing the inflammatory Th2, Th17 cytokines. These obtained results suggest that PNE has the promising strategy for immunotherapy in allergic rhinitis disease.

Topics: Allergens; Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Eosinophils; Fruit; Inflammation; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-kappa B; Ovalbumin; Piper nigrum; Plant Extracts; Protective Agents; Rhinitis, Allergic; Signal Transduction; STAT3 Transcription Factor; Th17 Cells; Th2 Cells

CD4. A murine model of AR was established using ovalbumin (OVA), and OVA-induced ILC2s were sorted and purified from the mouse nasal-associated lymphoid tissue (NALT), and cultured in vitro. Then, the expression of major histocompatibility complex class II (MHCII) on ILC2s was examined. CD4. We showed that ILC2s could be induced by OVA in the mouse NALT. The number and percentage of ILC2s in AR mice were increased. MHCII was expressed on ILC2s, and its protein and mRNA were all enhanced in allergic condition. IL-5 and IL-13 proteins and mRNAs were elevated after CD4. These findings show that CD4

Topics: Animals; CD4-Positive T-Lymphocytes; Disease Models, Animal; Histocompatibility Antigens Class II; Immunity, Innate; Interleukin-13; Interleukin-5; Leukocytes, Mononuclear; Lymphocytes; Lymphoid Tissue; Mice; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic

Allergic rhinitis (AR) is a common upper airway allergic disease caused by allergens triggering a type 2 immune response. The imbalance of CD4+ T cell subsets is the essential immunological feature of AR, which is mainly characterized by the predominance of T helper (Th) 2 cells. Recent studies indicated that the anti-inflammatory factor interleukin (IL)-37 is involved in the immune regulation of AR. However, the mechanism of IL-37 acts on AR has not been fully elucidated. Thus, we sought to assess the protective role of IL-37 in AR and further explore the possible mechanism. An ovalbumin (OVA)-induced AR murine model was established. After IL-37 treatment, the allergic symptoms (sneezes and nasal rubbings), nasal mucosal infiltration with eosinophils, and serum IgE production were found significantly attenuated. For CD4+ T cell subsets, the proliferation and differentiation of Th2 and Th17 cells were restrained. The relevant effector cytokines of IL-4, IL-5, IL-6, and IL-17a protein expression and transcription factors GATA3 and RORγt mRNA levels were obviously decreased. However, IL-37 had no significant effect on Th1 and Treg response including in IFN-γ, IL-10, T-bet, and Foxp3 expression. Furthermore, IL-37 was found down-regulated the STAT6, STAT3, phospho-STAT6, and phospho-STAT3 expression. In conclusion, IL-37 alleviates allergic inflammation in AR possibly through repressing STAT6 and STAT3 signaling pathways.

Topics: Allergens; Animals; Cytokines; Disease Models, Animal; Eosinophils; Humans; Immunoglobulin E; Interleukin-1; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Signal Transduction; STAT3 Transcription Factor; STAT6 Transcription Factor; Th1 Cells; Th2 Cells

Rosae Multiflorae fructus has potent antioxidative, analgesic, and anti-inflammatory properties.. We investigated the immunomodulatory effect of Rosae Multiflorae fructus extract (RMFE) on allergic inflammation in an allergic rhinitis (AR) mouse model.. Mice were sensitized and intranasally challenged with ovalbumin (OVA), the Th1/Th2-related cytokines and histopathology were examinated after RMFE treatments. Primary cell culture from spleen and NALT was performed to evaluate RMFE effect on Th1/Th2 responses. Four active components of RMFE were determined using HPLC and then tested the inhibition on Th2 response.. Oral administration of RMFE inhibited the accumulation of eosinophils in nasal lavage fluid (NALF) and the nasal mucosa, goblet cells in the nasal epithelium, and mast cells in the respiratory region of the nasal cavity. Thus, the swelling of the nasal epithelium, nasal-associated lymphoid tissue (NALT), and lung tissue were ameliorated. Furthermore, the RMFE suppressed Th2-related cytokines, such as IL-4, IL-5, and IL-13 in NALF, NALT, and splenocytes, whereas the Th1-associated cytokine IL-12 was up-regulated by RMFE. We also revealed the active components of RMFE, such as ellagic acid, hyperoside, isoquercitrin, and miquelianin. They may inhibit IL-4 secretion in allergic responses.. RMFE may have therapeutic potential for treating AR by modulating the relationships between Th1/Th2 responses.

Topics: Animals; Disease Models, Animal; Fruit; Immunomodulation; Inflammation; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Plants, Medicinal; Rhinitis, Allergic; Rosa; Th2 Cells

As an osteoclast differentiation factor, receptor activator of NF-κB ligand (RANKL) is produced by various immune cells and may be involved in the pathogenesis of osteoporosis and inflammation. Although RANKL is expressed in most immune cells and tissues, it is not clear how this might affect allergic inflammation.. The roles of RANKL in allergic rhinitis (AR) were analysed in an ovalbumin (OVA)-induced animal model, human subjects, and a human mast cell line (HMC-1). Small interfering RNA experiments were performed in an OVA-induced AR model.. RANKL and RANKL receptor (RANK) were up-regulated in serum or nasal mucosal tissues of AR patients and AR mice. RANKL and RANK were colocalised in mast cells of nasal mucosa tissue. Depletion of RANKL by RANKL siRNA ameliorated AR symptoms and reduced AR-related biomarkers, including thymic stromal lymphopoietin (TSLP), IgE, histamine, and inflammatory cell infiltration, whereas recombinant RANKL increased AR responses and TSLP levels. In addition, functional deficiency of TSLP decreased AR responses induced by RANKL. In human mast cells, interaction of RANKL with RANK increased production of TSLP and inflammatory cytokines. Production of TSLP by RANKL stimulation was mediated through activation of the PI3K, MAPK, caspase-1, and NF-κB pathways. Furthermore, dexamethasone alleviated RANKL-induced inflammatory reactions in AR models.. Collectively, these data suggest that RANKL may induce development of AR through up-regulation of TSLP.

Topics: Animals; Cell Line; Cytokines; Disease Models, Animal; Female; Humans; Male; Mast Cells; Mice, Inbred BALB C; Nasal Mucosa; Osteoclasts; Osteogenesis; Ovalbumin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Rhinitis, Allergic; RNA, Small Interfering; Signal Transduction; Thymic Stromal Lymphopoietin

Allergic rhinitis is a common allergic disease resulting from inappropriate Th2 cell-mediated immune responses to environmental antigens. As such, regulatory B cells and T helper cells play a critical role in the occurrence and development of allergic rhinitis.. Wild-type mice received ovalbumin (OVA) intranasal challenge for varied lengths of time, then the inflammatory state of their nasal mucosa was analyzed by histology. Changes to the proportion and function of TGF-β1. The most severe inflammatory response was observed in the mucosal tissue, where the percentage of TGF-β1. TGF-β1

Topics: Allergens; Animals; B-Lymphocytes, Regulatory; Disease Models, Animal; Eosinophils; Flow Cytometry; Humans; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; T-Lymphocytes, Regulatory; Th1-Th2 Balance; Th2 Cells; Transforming Growth Factor beta1

Sublingual immunotherapy (SLIT) is an established efficacious approach for the treatment of allergic rhinitis (AR). However, SLIT requires a long administration period to establish stable and adequate responses. This study investigated the efficacy of the sublingual administration of an allergen with liposomes enclosing α-GalCer (α-GC-liposome) as a potential adjuvant in mice with AR.. Mice with AR induced by OVA received the sublingual administration of OVA, α-GC-liposomes, or OVA plus α-GC-liposomes for 7 days. After nasal re-challenge with OVA, nasal symptoms were evaluated. The serum levels of OVA-specific Ig, the cytokine production of CD4. Although IL-4, IL-5 and IL-13 production from CD4. Our findings suggest that the sublingual administration of an allergen with α-GC-liposomes as an adjuvant might increase the therapeutic efficacy and effectiveness of this treatment method.

Topics: Adjuvants, Immunologic; Allergens; Animals; Cytokines; Disease Models, Animal; Galactosylceramides; Immunoglobulin E; Immunoglobulin G; Liposomes; Male; Mice, Inbred C57BL; Mice, Mutant Strains; Ovalbumin; Rhinitis, Allergic; Sublingual Immunotherapy; Th17 Cells; Th2 Cells; Treatment Outcome

The aim of this study was to evaluate the effect of topical administration of onion (Allium cepa) extract on nasal cavity for treatment of allergic rhinitis (AR). BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and challenged with intranasal instillation of OVA with or without onion extracts for five times a week on 3 consecutive weeks. Allergic symptom score according to frequencies of sneezing, serum total and OVA specific immunoglobulin E (IgE) level, cytokine levels of nasal mucosa and eosinophilic infiltration were analyzed. Allergic symptom score, serum total and OVA specific IgE, cytokine levels of nasal mucosa (interleukin (IL)-4, IL-5, IL-10, IL-13, IFN-γ, TNF-α and COX-2) and eosinophilic infiltration were higher in allergic mouse group than negative control group. Topical application of onion extracts significantly reduced allergic symptoms and OVA specific IgE levels. Cytokine levels of IL-4, IL-5, IL-10, IL-13 and IFN-γ were significantly decreased in groups treated with onion extract. In addition, eosinophil infiltration of nasal turbinate mucosa was also significantly decreased after treatment with onion extract. Topical administration of onion extract significantly reduces allergic rhinitis symptom and allergic inflammatory reaction in a murine allergic model. It can be assumed that the topical application of onion extract regulates allergic symptoms by suppressing the type-1 helper (Th1) and type-2 helper (Th2) responses and reducing the allergic inflammatory reaction.

Topics: Administration, Topical; Animals; Cytokines; Eosinophils; Female; Inflammation; Mice; Mice, Inbred BALB C; Onions; Ovalbumin; Plant Extracts; Rhinitis, Allergic

Bupleurum chinense is distributed in East Asia and has been used as a traditional herbal medicine for more than a thousand years. Though B. chinense has been reported to have immunomodulatory, anti-inflammatory, anti-oxidant, hepato-protective, antipyretic, analgesic and antifibrotic effects, its specific effect on allergic rhinitis disease has not been clarified. In this study, we investigated the anti-allergic and anti-inflammation effects of B. chinense extract (BCE) in an ovalbumin (OVA)-induced allergic rhinitis (AR) mouse model. Oral administration of BCE in a dose-independent manner regulated the balance of Th1/Th2/Treg cell differentiation in AR mice. Accordingly, BCE attenuated the expression of Th2-related cytokines such as IL-4, IL-5 and IL-13 in nasal lavage fluid (NALF) and nasal tissue and up-regulated the secretion of Th1/Treg cells including IL-10, IL-12 and IFN-

Topics: Animals; Bupleurum; Cell Differentiation; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Eosinophils; Inflammation Mediators; Male; Mast Cells; Mice, Inbred BALB C; Nasal Lavage Fluid; Ovalbumin; Phytotherapy; Plant Extracts; Rhinitis, Allergic; T-Lymphocytes, Regulatory; Th1 Cells; Th2 Cells

Nonylphenol (NP) is a widely distributed, toxic endocrine-disrupting chemical exhibiting estrogenic activity. However, its effect on allergic rhinitis (AR) remains unclear. In this study, the effects of NP on a murine model of AR were investigated. Mice were divided into ovalbumin (OVA), NP, and control groups. OVA was used for sensitization and challenge. Mice in the NP group were administered NP during the sensitization period. Allergic nasal symptoms and eosinophil counts in nasal mucosa were measured. Serum levels of OVA-specific IgE were determined by enzyme-linked immunosorbent assay. The mRNA levels of transcription factors of Th cells were determined with real-time polymerase chain reaction. Th cell subtypes and Treg numbers were counted with the aid of multi-color flow cytometry. Cytokine concentrations in nasal mucosa were determined using the cytometric bead array method. Subcutaneous injection of NP into mice exhibiting AR enhanced not only the nasal allergic symptoms, but also eosinophil infiltration and OVA-specific IgE. Moreover, NP upregulated IL-4, IL-5, IL-13, IL-9, IL-6 and IL-17, and downregulated IL-10, in the AR mouse model; IFN-γ and IL-23 were not affected. Transcription factors and Th cell percentages were evaluated to determine whether NP regulates Th cell subtypes in an AR mouse model. GATA3, PU.1, and RORγt levels were significantly increased, but FoxP3 and Helios were decreased. In addition, Th2, Th9, and Th17 subtype percentages significantly increased, and Treg cell percentages decreased, in NP administration groups; the percentage of Th1 subtypes was not affected. NP enhanced allergic inflammation in the AR mouse model through upregulation of Th2, Th9, and Th17 responses and negative regulation of Treg responses. These results suggest that NP may be trigger AR.

Topics: Air Pollutants; Allergens; Animals; Cytokines; Disease Models, Animal; GATA3 Transcription Factor; Gene Expression Regulation; Humans; Immunomodulation; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Phenols; Rhinitis, Allergic; T-Lymphocytes, Regulatory; Th17 Cells; Th2 Cells

Predominantly, 2 animal models are used for allergic rhinitis (AR), which are established by intraperitoneal (IP) injection plus local challenge and nasal-only delivery. The differences between these 2 models are not fully understood. Moreover, dose-response relationship to allergens remains unclear.. In this study, mice were sensitized by nasal drops (without adjuvant, once daily for 9 weeks) to set up a nasal-only delivery AR model. Five different doses of ovalbumin (OVA) nasal drops were served to explore the dose-response to allergens. Allergic symptoms, serum antibodies (IgE, IgG2a, and IgG1), spleen supernatant and nasal lavage fluid (NALF) cytokines (IL-4, IL-5, and IFN-r), and infiltrated eosinophils of the nasal mucosa were observed.. The allergic symptoms, serum antibodies, cytokines, and infiltrated eosinophils were significantly higher in the high OVA concentration compared with those of the control group. Different OVA concentrations associated with the severity of allergy. Within a certain concentration range, OVA concentration positively related to the severity of symptoms, IgE antibody level, and Th2 bias. Meanwhile, serum antibodies (IgE and IgG1) and cytokines (IL-4, IL-5 in spleen and IL-4 in NALF) were significantly higher in the classical IP injection group than in the nasal drip groups.. The IP injection model and the nasal-only delivery model are 2 typical models for AR that causes a different immune response. A positive dose-response relationship in the nasal-only delivery model is observed from 25 mg/mL to 0.025 mg/mL.

Topics: Administration, Intranasal; Allergens; Animals; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Eosinophils; Female; Immunoglobulin E; Injections, Intraperitoneal; Mice, Inbred BALB C; Nasal Lavage Fluid; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic

AST2017-01 is developed to be used for treatment and prevention of allergic diseases and composed of processed-Cordyceps militaris and processed-Rumex crispus. But, effect of AST2017-01 remains unclear in an allergic rhinitis (AR). So, this study aimed to explore the effects of AST2017-01 in ovalbumin (OVA)-induced AR animal model.. OVA-induced AR animals were orally administered AST2017-01 and chrysophanol, an active component of AST2017-01 for 10 days.. In mice with AR, AST2017-01 and chrysophanol markedly decreased number of rubs, IgE, histamine, thymic stromal lymphopoietin, tumor necrosis factor-α, interleukin (IL)-1β, IL-4, IL-5, and IL-13 in serum or nasal mucosa tissues. Moreover, activities and protein levels of caspase-1 were markedly diminished by oral administration of AST2017-01 and chrysophanol. Declines of macrophage inflammatory protein-2, intercellular adhesion molecules-1, eosinophil, and mast cells were also noted in nasal mucosa tissues of AST2017-01 and chrysophanol groups.. Taken together, these findings indicate that AST2017-01 has an anti-allergic effect as a therapeutic agent or functional food for treating and preventing AR.

Topics: Animals; Anthraquinones; Anti-Allergic Agents; Caspase 1; Cordyceps; Cytokines; Disease Models, Animal; Eosinophils; Female; Mast Cells; Mice, Inbred BALB C; Nasal Mucosa; Neutrophils; Ovalbumin; Plant Preparations; Rhinitis, Allergic; Rumex

Allergic rhinitis (AR) is an allergic nasal disease characterized by nasal obstruction, rhinorrhea, sneezing, and itching. Type 1 helper T cells (Th1)/type 2 helper T cells (Th2) imbalance has been identified as an important immunological mechanism of AR. In addition, up-regulation of type 17 helper T cells (Th17) also increase the risk of developing AR. Gallic acid (3, 4, 5-trihydroxybenzoic acid, GA), a polyphenol natural product, is obtained from various herbs, red wine, and green tea. It is known to have diverse biological effects such as anti-oxidation, anti-inflammation, anti-microbial and anti-cancer. In the present study, the effect of GA on airway inflammation and expression of Th1, Th2 and Th17 cytokines in an ovalbumin (OVA)-induced AR mouse model were investigated. GA alleviated the nasal allergic symptoms, reduced the thickness of nasal mucosa, attenuated goblet cell hyperplasia and eosinophil cell infiltration in the nasal mucosa, decreased the levels of interleukin (IL)-4, IL-5, IL-13 and IL-17 in nasal lavage fluid (NALF), and diminished the levels of OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a in serum. However, GA increased the expression of interferon-gamma and IL-12 in NALF. Taken together, it suggests that GA may be used as a therapeutic agent for AR.

Topics: Allergens; Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Eosinophils; Gallic Acid; Humans; Immunoglobulin E; Inflammation; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Th1 Cells; Th17 Cells; Th2 Cells

Topics: Animals; Anti-Inflammatory Agents; Astragalus propinquus; Cytokines; Disease Models, Animal; Female; Mice, Inbred BALB C; Nasal Mucosa; NF-kappa B p50 Subunit; Ovalbumin; Phytotherapy; Plant Preparations; Rhinitis, Allergic; T-Lymphocytes, Regulatory; Transcription, Genetic

Clinical data show that part of patients with sinonasal diseases suffered from olfactory dysfunction, especially with allergic rhinitis (AR) and chronic rhinosinusitis (CRS). However, the mechanisms responsible for AR-induced olfactory loss are still largely unknown. Because of the difficulty to obtain human olfactory mucosa, an AR-induced olfactory loss animal model needs to be constructed to clarify the mechanism. The AR mouse model was induced by intraperitoneal sensitizing with ovalbumin (OVA) followed by intranasal challenge lasted from 1 to 12 weeks. For groups with recovery, mice were housed for another 4-week long without any treatment after the last intranasal challenge. Olfactory function, olfactory receptor neurons (ORNs) density and leukocytes infiltration were examined at different time points. Olfactory loss occurs immediately after 1-week intranasal challenge and deteriorates almost to anosmia after 8th week, and after that olfactory loss become irreversible. Nasal inflammation induces significant infiltration of leukocytes into olfactory epithelium (OE), which negatively correlated with the density of ORNs and mouse olfaction in a time dependent manner. The neutrophilic subtype dominates in number amongst the total infiltrated leukocytes, indicating its pivotal role in nasal inflammation-induced olfactory dysfunction. In this study, we constructed a persistent AR-induced olfactory loss mouse model, losing the ability to recover from dysfunction if the disease duration more than eight weeks, which implies that timely treatments are necessary. Meanwhile, this mouse model could provide an easy and reliable system to clarify the mechanisms of AR-induced irreversible olfactory dysfunction.

Topics: Animals; Disease Models, Animal; Leukocytes; Male; Mice; Mice, Inbred BALB C; Olfaction Disorders; Olfactory Receptor Neurons; Ovalbumin; Rhinitis, Allergic; Smell

This study aimed to investigate the effect of the p38 mitogen-activated protein kinase (p38MAPK) signaling pathway on olfactory mucosa function and apoptosis of olfactory sensory neurons (OSNs) in an allergic rhinitis (AR) mouse model.. Fifty-five BALB/c mice were used to establish AR models by ovalbumin, and their olfactory function was confirmed by the buried food pellet test. Then, 28 mice with hyposmia were selected. SB203580, a p38MAPK inhibitor, and normal saline (NS) were injected into mice with olfactory defects. The olfactory function, apoptosis of OSNs in olfactory mucosa, and the expression of the olfaction marker protein (OMP), p38MAPK, and p-p38MAPK were detected after the intervention.. SB203580 treatment significantly upregulated OMP expression and significantly improved the olfactory function of AR mice by reducing the percentage of apoptotic OSNs. In addition, SB203580 attenuated the activation of the p38MAPK signaling pathway.. SB203580 protected olfactory function in an AR mouse model. This protective effect may be associated with the antiapoptotic effects of SB203580 via the p38MAPK signaling pathway.

Topics: Animals; Apoptosis; Female; Imidazoles; Irritants; MAP Kinase Signaling System; Mice, Inbred BALB C; Olfaction Disorders; Olfactory Receptor Neurons; Ovalbumin; p38 Mitogen-Activated Protein Kinases; Protein Kinase Inhibitors; Pyridines; Rhinitis, Allergic; Signal Transduction; Smell

Topics: Animals; Antigens, Plant; B-Lymphocytes; B7-2 Antigen; CD40 Antigens; Dendritic Cells; Gene Silencing; Hypersensitivity; Immunization; Immunoglobulin E; Interleukin-4; Interleukin-5; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Plant Proteins; Rhinitis, Allergic

The present study aims to investigate the effects of toll-like receptor 4 (TLR4) antagonist in an ovalbumin (OVA)-induced mouse model of combined allergic rhinitis and asthma syndrome (CARAS). An OVA-induced mouse model of CARAS was established and TLR4 antagonist, TAK-242, was administrated intranasally or intraperitoneally. The number of sneezing and nasal rubbing was counted. The frequency of different cell types in the bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NLF) was analyzed using flow cytometry. Expressions of protein in nasal mucosa and lungs were determined using western blotting. Levels of interleukin (IL)-4, IL-5, and IL-13 were determined using Enzyme-linked Immunosorbent Assay (ELISA). Histological scores were applied for the assessment of lung injury. Treatment of TAK-242 downregulated CCL2 expression and reduced monocyte infiltration in nasal mucosa and lung tissues. Additionally, treatment of TAK-242 ameliorated upper airway symptoms including the sneezing and nasal rubbing by the regulation of cytokines including IL-4, IL-5, and IL-13. Furthermore, treatment of TAK-242 ameliorated lower airway symptoms including decreasing the frequency of CD45

Topics: Animals; Anti-Inflammatory Agents; Asthma; Cytokines; Disease Models, Animal; Female; Lung; Mice, Inbred BALB C; Monocytes; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sulfonamides; Syndrome; Toll-Like Receptor 4

What is the central question of this study? What is the mechanism of DNA methylation in allergic rhinitis? What is the main finding and its importance? A miR-199-3p-Dnmt3a-STAT3 signalling pathway is involved in ovalbumin-induced allergic rhinitis, and miR-199-3p antagomir can relieve the symptoms in the mouse model.. Recent research has pointed out the involvement of epigenetic modifications in allergic rhinitis (AR), especially DNA methylation. However, the detailed mechanism has remained largely uncovered. We used ovalbumin (OVA) to induce AR in mouse, and behaviour scores were used to confirm its successful establishment. Histamine and other inflammatory factors were detected to further verify success of the model. Real-time PCR was employed to identify the overexpression of miR-199-3p and subsequent down-regulation of DNA methyltransferase 3a (Dnmt3a). Western blotting was utilized to detect Dnmt3a and signal transducer and activator of transcription 3 (STAT3) at the protein level. Bisulfite sequencing PCR was applied to reveal the methylation status of the Stat3 promoter region. A dual-reporter assay was used to confirm the direct targeting of miR-199-3p on the Dnmt3a mRNA and an antagomir specific to miR-199-3p was injected to rescue the symptoms of AR. The AR model was successfully established in mouse and confirmed by both behaviour and molecular markers. We also found lowered expression of Dnmt3a and consecutive hypomethylation of Stat3 promoter and elevated expression of STAT3, which then led to overexpression of IgE and other inflammatory factors. MicroRNAs that worked on the Dnmt3a 3'-untranslated region were predicted and then verified by dual-reporter assay. Finally injection of a miR-199-3p antagomir successfully attenuated the symptoms of AR. We propose that the miR-199-3p-Dnmt3a-STAT3 signalling pathway is involved in OVA-induced AR.

Topics: 3' Untranslated Regions; Animals; Cell Line; Disease Models, Animal; DNA (Cytosine-5-)-Methyltransferases; DNA Methylation; DNA Methyltransferase 3A; Humans; Mice; Mice, Inbred BALB C; MicroRNAs; Ovalbumin; Rhinitis, Allergic; Signal Transduction; STAT3 Transcription Factor

Chinese herbs such as

Topics: Animals; Asteraceae; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Therapy, Combination; Drugs, Chinese Herbal; Humans; Magnoliaceae; Male; Nasal Mucosa; Oils, Volatile; Ovalbumin; Protein Interaction Maps; Rats; Rhinitis, Allergic; Treatment Outcome

Airway hyperresponsiveness (AHR) has been proposed as a feature of pathogenesis of eosinophilic upper airway inflammation such as allergic rhinitis (AR). The measurement system for upper AHR (

Topics: Animals; Disease Models, Animal; Female; Inflammation; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Respiratory Hypersensitivity; Rhinitis, Allergic; X-Ray Microtomography

Acetylshikonin has long been known as an anti-inflammatory and antioxidative reagent. However, the anti-allergic effect has not been studied. The aim of this study was to evaluate the effect of acetylshikonin on allergic rhinitis (AR) in mice. Mice were sensitized by intraperitoneal injection of OVA and aluminum hydroxide and challenged with intranasal instillation of OVA. Acetylshikonin was administered orally after nasal cavities challenge. Severity of allergic rhinitis was assessed according to nasal symptoms; serum OVA-specific immunoglobulin E (IgE), IgG1, and IgG2a level; and interleukin (IL)-4, IL-10, IL-5, IL-13, TNF-α, IL-12, and interferon (INF)-γ levels in nasal lavage fluid (NALF). Additionally, the histological change and the release of histamine in serum and nasal lavage fluid were evaluated by acid-Schiff stain and ELISA. Acetylshikonin attenuated manifestation of nasal symptoms in sensitized mice and inhibited production of Th2-related OVA-specific IgE, IgG1, and Th2 cell-produced IL-4, IL-5, IL-13, and mast cell produced histamine; however, it had no effect on Th1 cell-produced cytokines, like INF-γ. In addition, the degree of inflammatory cell infiltration and goblet cell hyperplasia was attenuated by acetylshikonin treatment. Our results suggest that acetylshikonin effectively reduces allergic inflammation in a mouse model of allergic rhinitis by its anti-allergic and anti-inflammatory properties.

Topics: Administration, Oral; Allergens; Animals; Anthraquinones; Cytokines; Disease Models, Animal; Histamine Release; Immunologic Factors; Injections, Intraperitoneal; Mast Cells; Mice; Ovalbumin; Rhinitis, Allergic; Th2 Cells; Treatment Outcome

It is well known that CD4+CD25+Foxp3+Treg cells play an important role in the development of allergic rhinitis (AR); the defect of cell numbers and functions contribute to AR. Hydrogen has been proven effective in alleviating symptoms of AR. We herein aim to verify the protective effects of hydrogen on CD4+CD25+Foxp3+Treg cells in guinea pigs with AR and to explore the effect of hydrogen-rich saline (HRS) on CD4+CD25+Foxp3+Treg cells in animals with AR and investigate the underlying anti-inflammatory mechanism. Eighteen guinea pigs were randomly divided into three groups (control group/AR group/AR-HRS group). The guinea pigs were injected with hydrogen-rich saline (AR-HRS group) for 10 days after sensitization. The control group was injected with an equal volume of normal saline. The number of sneezes, degree of runny nose, and nasal-rubbing movements were scored. Peripheral blood eosinophil count was recorded. The proportions of Th1/Th2 of the peripheral blood and the CD4+CD25+Foxp3+T cells in the CD4+T cells of the spleen and peripheral blood were determined by flow cytometry. The content of interleukin (IL)-10 and transforming growth factor (TGF)-β in the serum was detected by enzyme-linked immunosorbent assay (ELISA). The protein and mRNA expression of Foxp3, IL-10, and TGF-β were determined by Western blot, immunofluorescence, and real-time PCR analysis, respectively. Scores of symptoms, number of eosinophils,and nasal mucosa damage were dramatically reduced after HRS treatment. HRS increased the expression of Foxp3, IL-10, TGF-β, and number of CD4+CD25+Foxp3+Treg cells, which were reduced in AR. HRS also revised the dysregulation of Th1/Th2 balance. Both the number and biological activity of CD4+CD25+Foxp3+Treg cells increased with up-regulation of Th1/Th2 after HRS administration. HRS could play a protective role in attenuating AR through improving the proportion and functions of CD4+CD25+Foxp3+Treg cells.

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Eosinophils; Forkhead Transcription Factors; Guinea Pigs; Interleukin-10; Male; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Signal Transduction; Sodium Chloride; Spleen; T-Lymphocytes, Regulatory; Th1 Cells; Th1-Th2 Balance; Th2 Cells; Transforming Growth Factor beta

Intranasal immunization with phosphorylcholine (PC) is known to reduce immunoglobulin (Ig)E production. However, its effects on the occurrence of allergic rhinitis (AR) are unknown. This study was performed to evaluate the effects of PC-keyhole limpet hemocyanin (PC-KLH) and to examine the effects on the occurrence of AR in a murine model of AR.. In vivo study using an animal model.. Forty-five female BALB/c mice were divided into three groups; those pretreated with intranasal administration of PC-KLH followed by intraperitoneal sensitization and nasal challenge with ovalbumin (OVA) (group A), those untreated with PC-KLH followed by sensitization and nasal challenge with OVA (group B), and those untreated with PC-KLH or OVA as controls (group C). Nasal symptoms, allergic inflammation in the nasal mucosa, OVA specific IgE production, and cytokine profile were compared among those three groups. Dendritic cells (DCs) were isolated from splenic cells and PC-KLH-stimulated interleukin (IL)-12p40 production was measured.. The mice pretreated with PC-KLH showed lower allergic nasal symptoms and inflammation compared to untreated mice. The levels of total IgE and OVA-specific IgE in serum, and IL-4 production by nasal and splenic CD4. Intranasal administration of PC-KLH suppressed allergic inflammation in nasal mucosa and antigen-specific IgE production by downregulating Th2-type immune response. Intranasal immunization with PC might be useful to prevent AR and upper airway bacterial infection.. NA. Laryngoscope, 128:E234-E240, 2018.

Topics: Adjuvants, Immunologic; Administration, Intranasal; Animals; Cytokines; Dendritic Cells; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Hemocyanins; Immunoglobulin E; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Phosphorylcholine; Rhinitis, Allergic

This study aims to establish an experimental mouse model of minimal persistent inflammation (MPI), observe the features of inflammation and hyper-responsiveness of the upper/lower airways, and explore the relationship between inflammation and hyper-responsiveness in the upper/lower airways.. Sixty-four female BALB/c mice were randomly divided into four groups: allergic rhinitis (AR) group as positive control, MPI group, negative control group and blank control group. Mice were given high and low-concentrated ovalbumin solution after basic and intensive sensitization to establish AR model and MPI model. Nasal mucosa and lung tissues were stained to observe eosinophil infiltration, goblet cell hyperplasia, and expression of intercellular adhesion molecule 1 (ICAM-1). Airway hyper-responsiveness was assessed. Levels of specific immunoglobulin E (sIgE), interleukin (IL)-4 and IL-5 in peripheral blood, nasal lavage fluid (NLF), and bronchoalveolar lavage fluid (BALF) were detected by Enzyme-linked immunosorbent assay.. The eosinophil infiltration and expression of ICAM-1 on nasal mucosa and in lung tissues in the AR and MPI groups were significantly elevated compared to control groups. Goblet cells count increased only in the nasal mucosa and not in lung tissues. Eosinophil and neutrophil count of NLF and BALF in the AR and MPI groups increased significantly compared to control groups. Level of IL-4 did not increase significantly, but sIgE and IL-5 did.. Mice in the MPI status exhibits lower airway inflammation and hyper-responsiveness with increase in eosinophil count, goblet cells, ICAM-1, IL-4, and IL-5. These results provide further evidence for the importance of MPI of AR in lower airway diseases.

Topics: Animals; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Eosinophils; Female; Goblet Cells; Immunoglobulin E; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-4; Interleukin-5; Lung; Mice; Mice, Inbred BALB C; Nasal Lavage Fluid; Nasal Mucosa; Ovalbumin; Respiratory Hypersensitivity; Rhinitis, Allergic

Background Mometasone furoate, one of the second generation intranasal corticosteroids, is currently used in suspension form due to its poor solubility. However, this is not favorable for nasal application because of the rapid elimination of the instilled drug from the nasal cavity by mucociliary clearance and delayed onset of action due to the slow dissolution of drug in suspension. Objective The aim of this study was to determine the antiallergic effects of mucoadhesive thermosensitive in situ gel containing mometasone furoate that we developed previously to prolong the contact between the drug and nasal mucosa and to prevent drainage of the formulation in an ovalbumin-induced rat model of allergic rhinitis. Methods An experimental allergic rhinitis model was developed in female Wistar albino rats by intraperitoneal injection of ovalbumin every 2 days for 14 days followed by its repeated intranasal instillation for 7 consecutive days. Intranasal instillation of ovalbumin was continued every other day for 14 days. Mometasone furoate in situ gel (5 μg/10 µl), mometasone furoate suspension (5 μg/10 µl), and physiological saline (10 µl) were administered into the bilateral nasal cavities from day 22 to day 35. Antiallergic effects were evaluated through histopathological evaluation, analysis of ovalbumin-specific serum immunoglobulin E, and a symptom score. Results Mometasone furoate in situ gel significantly decreased the nasal symptoms and ovalbumin-specific serum immunoglobulin E level as compared with mometasone furoate suspension and physiological saline. Additionally, inflammatory histological symptoms such as mucosal edema, vascular dilatation, eosinophil infiltration, and loss of cilia within the nasal mucosa of allergic rhinitis model rats were remarkably improved with the treatment of mometasone furoate in situ gel. Conclusion These results suggest that mometasone furoate in situ gel has a better therapeutic potential for the treatment of allergic rhinitis compared to mometasone furoate suspension.

Topics: Administration, Intranasal; Animals; Anti-Allergic Agents; Disease Models, Animal; Female; Gels; Immunoglobulin E; Mometasone Furoate; Nasal Cavity; Ovalbumin; Rats; Rats, Wistar; Rhinitis, Allergic; Temperature; Treatment Outcome

The experimental model of combined allergic rhinitis and asthma syndrome (CARAS) has shown that CpG oligodeoxynucleotides (CpG-ODNs) are potential inhibitors of type 2 helper cell-driven inflammatory responses. Currently available CpG-ODNs modestly inhibit allergic responses in CARAS, while a combination strategy for upper airway treatment by co-administration of CpG-ODNs and glucocorticoids may show good efficacy. This study aimed to assess the therapeutic effects of CpG-ODNs combined with budesonide (BUD) on upper and lower-airway inflammation and remodeling in mice with CARAS induced by chronic exposure to ovalbumin (OVA), exploring the possible underlying molecular mechanisms. A BALB/c mouse model of chronic CARAS was established by systemic sensitization and repeated challenge with OVA. Treatment with CpG-ODNs or BUD by intranasal administration was started 1 h after OVA challenge. Then, nasal mucosa and lung tissues were fixed and stained for pathologic analysis. The resulting immunologic variables and TSLP-DC-OX40L axis parameters were evaluated. Both CpG-ODNs and BUD intranasal administration are effective on reducing Th2-type airway inflammation and tissue remodeling. Co-administration of CpG-ODNs and BUD was more effective than each monotherapy in attenuating upper and lower-airway inflammation as well as airway remodeling in chronic CARAS. Notably, combination of CpG-ODNs with BUD modulated the TSLP-DC-OX40L axis, as demonstrated by decreased TSLP production in the nose and lung, alongside decreased TSLPR and OX40L in DC. Intranasal co-administration of CpG-ODNs and BUD synergistically alleviates airway inflammation and tissue remodeling in experimental chronic CARAS, through shared cellular pathways, as a potent antagonist of the TSLP-DC-OX40L axis.

Topics: Airway Remodeling; Animals; Asthma; Budesonide; Cytokines; Drug Synergism; Inflammation; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Oligodeoxyribonucleotides; Ovalbumin; OX40 Ligand; Rhinitis, Allergic; Thymic Stromal Lymphopoietin; Tumor Necrosis Factor Inhibitors

Growing evidence indicates that the Toll-like receptor7/8(TLR7/8) agonist resiquimod (R848) is a potential inhibitor of type-2 immunity. However, the mechanisms mediating its therapeutic effects are not fully understood. This study investigated the effects of R848 on OVA-induced allergic rhinitis(AR) mice and the expression of IL-25, IL-33, TSLP, T-cell immunoglobulin mucin1 (TIM1) and T-cell immunoglobulin mucin3 (TIM3). BALB/c mice were intranasally sensitized and challenged with ovalbumin (OVA), and R848 was intraperitoneally injected into AR mice. Histological changes in the nasal mucosa were evaluated by hematoxylin and eosin (H & E) and Periodic Acid-Schiff (PAS) staining; cytokine levels in serum were measured with enzyme-linked immunosorbent assays (ELISAs);the mRNA expression levels of IFN-γ, IL-17 and Foxp3 in the spleen determined by quantitative real-time RT-PCR (qRT-PCR); the proportions of Th1, Th2, Th17, Treg and TIM3 + IFN-γ + Th1 cells in the spleen were assessed with flow cytometry; TIM1, TIM3 and IL-33 expression levels in the nasal mucosa were evaluated with immunofluorescence staining(IF).R848 alleviated the nasal allergic symptoms; reduced eosinophil cell infiltration, goblet cell hyperplasia in the nasal mucosa; reduced IL-13, IL-17, IL-25 and IL-33 levels in serum; upregulated the relative mRNA expression of IFN-γ and Foxp3, and downregulated the relative mRNA expression of IL-17 in the spleen; decreased Th2, Th17 and TIM3 + IFN-γ + Th1 cells ratios, increased the proportion of Th1 and Treg cells in the spleen; suppressed TIM1 and TIM3,but increased IL-33 expression in the nasal mucosa in OVA-induced AR mice. R848 suppresses IL-25, IL-33 released and TIM1, TIM3 expression, which may contribute to its anti-allergic effects.

Topics: Animals; Anti-Allergic Agents; Antigens; Cytokines; Disease Models, Animal; Female; Hepatitis A Virus Cellular Receptor 1; Hepatitis A Virus Cellular Receptor 2; Imidazoles; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Spleen

Conventional allergic rhinitis (AR) treatments have limitations due to the lack of safety and complete cure strategy. We evaluated the effects of silent information regulator 1 (SIRT1), a multifunctional molecule involved in a variety of inflammatory pathways, on murine AR model. Ovalbumin (OVA)-induced murine model was constructed, and recombinant SIRT1 was administered into the nostril continuously. The expression of SIRT1 was measured at mRNA and protein levels, and the allergic symptoms were evaluated. Protein levels of OVA-specific IgE, leukotriene C4 (LTC4), eosinophil cation protein (ECP), prostaglandin D2 (PGD2), as well as different inflammatory cytokine mediators in the serum and nasal lavage fluid (NLF), were assessed by ELISA. The effects of SIRT1 on human primary nasal epithelial cells challenged with tumour necrosis factor (TNF)-α were also evaluated by investigating the HMGB1/TLR4 signalling pathway. Administration of SIRT1 significantly alleviated OVA-induced AR symptoms with lower numbers of sneezing and nasal rubbing events, decreased levels of OVA-specific IgE, LTC4, ECP, PGD2, less inflammatory cells and downregulated levels of Th2 type cytokines. SIRT1 also reduced the genes of HMGB1/TLR4 signalling pathway in the murine model and cultured human nasal epithelial cells. Expression of SIRT1 is impaired in OVA-induced AR model. The administration of SIRT1 alleviates the allergic symptoms of mice, regulates the production of pro-inflammatory mediators predominantly produced by Th2 cells in AR and attenuates expressions of proteins relevant to HMGB1/TLR4 signalling pathway. All the results showed that SIRT1 is promising as a therapeutic agent of AR.

Topics: Animals; Cells, Cultured; Disease Models, Animal; Down-Regulation; Eosinophil Cationic Protein; Female; HMGB1 Protein; Humans; Immunoglobulin E; Leukotriene C4; Mice; Mice, Inbred BALB C; Nasal Lavage Fluid; Nasal Mucosa; Ovalbumin; Prostaglandin D2; Recombinant Proteins; Rhinitis, Allergic; Signal Transduction; Sirtuin 1; Th2 Cells; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Allergic inflammation is the foundation of allergic rhinitis and asthma. Although microRNAs are implicated in the pathogenesis of various diseases, information regarding the functional role of microRNAs in allergic diseases is limited. Herein, we reported that microRNA-302e (miR-302e) serves as an important regulator of allergic inflammation in human mast cell line, HMC-1 cells. Our results showed that miR-302e is the dominant member of miR-302 family expressed in HMC-1 cells. Moreover, the expression of miR-302e was significantly decreased in response to phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 or ovalbumin (OVA) stimulation. Overexpression of miR-302e blocked PMA/A23187 or OVA induced the increase in inflammatory cytokines levels, such as IL-1β, IL-6, tumor necrosis factor (TNF)-α and thymic stromal lymphopoietin, while miR-302 inhibition further promoted the release of these cytokines. Mechanistically, we found that miR-302e is a novel miRNA that targets RelA, a gene known to be involved in regulating inflammation, through binding to the 3'-UTR of RelA mRNA. Ectopic miR-302e remarkably suppressed the luciferase activity and expression of RelA, whereas down-regulation of miR-302e increased RelA luciferase activity and expression. Pharmacological inhibition of NF-κB reversed the augmented effect of miR-302e down-regulation on inflammatory cytokines level. Taken together, the present study demonstrates miR-302e limits allergic inflammation through inhibition of NF-κB activation, suggesting miR-302e may play an anti-inflammatory role in allergic diseases and function as a novel therapeutic target for the treatment of these diseases.

Topics: Calcimycin; Cell Line; Gene Expression Regulation; Humans; Inflammation; Mast Cells; MicroRNAs; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Tetradecanoylphorbol Acetate; Transcription Factor RelA

Thymic stromal lymphopoietin (TSLP) is a regulator of mast cell-mediated allergic inflammatory reactions, but the manner in which TSLP contributes to allergic rhinitis (AR) remains unclear.. Here, we sought to determine that TSLP plays a crucial role in AR by interacting with Src-type tyrosine kinase p56lck and STAT6 and promoting mast cells degranulation.. The effects of TSLP on mast cell degranulation and AR were analysed in human mast cell line (HMC-1 cells), ovalbumin (OVA)-induced AR animal model, and human subjects. Small interfering RNA experiments were performed in HMC-1 cells and OVA-induced AR model. Immune responses were analysed by enzyme-linked immunosorbent assay, Western blotting, immunoprecipitation, and histological studies.. Thymic stromal lymphopoietin levels and mast cell-derived p56lck activation were elevated in human subjects with AR, and in AR mice, exogenous TSLP accelerated TH2-allergic inflammatory reactions by up-regulating p56lck and STAT6. On the other hand, depletion of TSLP, p56lck, and STAT6 ameliorated clinical symptoms in AR mice. The selective inhibitor of p56lck, damnacanthal, inhibits AR reactions.. Collectively, these observations suggest a role for TSLP/p56lck/STAT6 in AR and offer insight into potential therapeutic strategies.

Topics: Anaphylaxis; Animals; Cell Degranulation; Cell Differentiation; Cell Line; Cytokines; Disease Models, Animal; Humans; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Mast Cells; Mice; Mice, Knockout; Ovalbumin; Rhinitis, Allergic; STAT6 Transcription Factor; Th2 Cells; Thymic Stromal Lymphopoietin

We investigated whether the therapeutic effects of dexamethasone for allergic asthma and rhinitis were enhanced in mice when exposed to hypergravity. Forty mice were divided into 5 groups (n = 8/group): Control group received saline intraperitoneally (i.p.) and intranasally (i.n.); Asthma group received i.p./i.n. ovalbumin (OVA) for inducing allergic asthma/rhinitis; Dexa group received i.n. dexamethasone (0.75 mg/kg) 30 minutes before each OVA challenge; Hypergravity group was subjected to allergic asthma/rhinitis as well as exposed to 5 G hypergravity for 30 days; Finally in Dexa/Hypergravity group, hypergravity and dexamethasone were used simultaneously during induction of allergic asthma/rhinitis. Dexa group and Hypergravity group showed a significant decrease in serum total IgE levels compared to the Asthma group (p<0.05). Dexa/Hypergravity group showed greater IgE decrease compared with Dexa group (p = 0.040). Compared with the monotherapy groups, Dexa/Hypergravity group showed significantly fewer eosinophils in BAL fluid (p<0.05). Dexa/Hypergravity group showed significantly decreased eosinophilic infiltration into the lungs and nasal cavity (p<0.05). EC-SOD (extracellular superoxide dismutase) expression was significantly upregulated in the Hypergravity group and Dexa/Hypergravity group, compared with the Dexa group (p<0.05). In conclusion, hypergravity enhanced the therapeutic effect of dexamethasone in a murine model of allergic asthma and rhinitis. Therefore, combination could be a promising strategy, and one of its mechanisms could be up-regulation of EC-SOD expression.

Topics: Animals; Anti-Allergic Agents; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Dexamethasone; Drug Evaluation, Preclinical; Enzyme Induction; Eosinophils; Female; Hypergravity; Lung; Lymphocytes; Mice; Mice, Inbred BALB C; Nasal Cavity; Neutrophils; Ovalbumin; Rhinitis, Allergic; Specific Pathogen-Free Organisms; Superoxide Dismutase; Up-Regulation

Allergic rhinitis (AR) is a major concern in personal and public health, which negatively affects emotions and behavior, leading to cognitive deficits, memory decline, poor school performance, anxiety, and depression. Several cellular and molecular mediators are released in the inflammatory process of AR and activate common neuroimmune mechanisms, involving emotionally relevant circuits and the induction of anxiety. Responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to allergic processes have been reported, which may also include responsiveness of the hippocampus, cortex, and other brain regions. Here, we have used an optimized rat model of AR to explore whether the disease has a relationship with inflammatory responses in the hippocampus. AR was established in adult rats by ovalbumin sensitization, and the expression of various inflammatory substances in the hippocampus was measured by specific assays. Comparison between experimental and various control groups of animals revealed an association of AR with significant upregulation of substance P, microglia surface antigen (CD11b), glial fibrillary acid protein (GFAP), tumor necrosis factor-

Topics: Animals; CD11 Antigens; Disease Models, Animal; Glial Fibrillary Acidic Protein; Hippocampus; Inflammation; Interleukin-6; Male; Ovalbumin; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Substance P; Tumor Necrosis Factor-alpha

Topics: Adjuvants, Immunologic; Allergens; Aluminum Hydroxide; Animals; B-Lymphocytes; Bronchoalveolar Lavage Fluid; CD40 Antigens; Cytokines; Dendritic Cells; Hemocyanins; Immunoglobulin E; Immunoglobulin G; Immunotherapy, Adoptive; Male; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; RNA, Small Interfering; Spleen

Allergic rhinitis (AR) is a global health problem because of its steadily increasing incidence and prevalence that currently affects about 30% of people worldwide. β-eudesmol has various beneficial effects, including anti-cancer and anti-allergic activities. However, the effects of β-eudesmol on AR have not yet been clarified; thus, we investigated the effects of β-eudesmol in an ovalbumin-induced AR animal model using enzyme-linked immunosorbent assay, histamine assay, Western blotting, and hematoxylin and eosin staining methods. β-eudesmol reduced the nasal rubs score and levels of histamine and immunoglobulin E in serum of AR mouse. In addition, the levels of thymic stromal lymphopoietin, interleukin-1β, tumor necrosis factor-α, and macrophage inflammatory protein-2 were down-regulated and infiltration of eosinophils and the level of intercellular adhesion molecule-1 were inhibited by β-eudesmol administration. β-eudesmol administration also reduced active caspase-1 and nuclear factor-κB DNA binding activity in nasal mucosa tissues of AR mice. Taken together, these results indicate that β-eudesmol would be effective for the treatment of allergic and inflammatory diseases, such as AR.

Topics: Animals; Body Weight; Caspase 1; Chemokine CXCL2; Cytokines; Disease Models, Animal; Down-Regulation; Eosinophils; Female; Interleukin-1beta; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Sesquiterpenes, Eudesmane; Signal Transduction; Thymic Stromal Lymphopoietin; Tumor Necrosis Factor-alpha

Geraniol is a monoterpene alcohol that has anti-fungal, anti-cancer and anti-nociceptive properties, but its anti-allergic rhinitis (AR) property is unclear.. In this study, the anti-inflammatory role and its possible mechanisms of geraniol in human mast cell line (HMC-1) cells stimulated by inflammatory trigger phorbol 12-myristate 13-acetate plus A23187 (PMACI), as well as in ovalbumin (OVA)-induced AR mice models were investigated.. PMACI results in a significant increase in the production of proinflammatory cytokines, such as TNF-α, IL-1β, MCP-1, IL-6 and as well as histamine. Geraniol was found to inhibit both TNF-α, IL-1β and IL-6 protein and mRNA expressions at concentrations of 40, 80, 160 μM. In OVA-induced AR models, geraniol treatment was able to suppress AR biomarkers (OVA-specific IgE and IL-1β as well as histamine) and nasal rub scores. Interestingly, p38, a member of the mitogen-activated protein kinase (MAPK) signaling family, was found to be increasingly hypophosphorylated as geraniol dose was increased. Similar decreases in the nuclear level of p65, a member of the nuclear factor kappa B (NF-κB) signaling pathway, were also observed.. Our data highlights that the anti-inflammatory properties of geraniol on AR-related markers in activated HCM-1 cells and OVA-induced AR models may be mediated through the regulation of the MAPK/NF-κB signaling pathway.

Topics: Acyclic Monoterpenes; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Calcimycin; Cell Line; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Histamine; Humans; Inflammation Mediators; Mice; Mice, Inbred BALB C; Molecular Structure; Ovalbumin; Rhinitis, Allergic; Structure-Activity Relationship; Terpenes; Tetradecanoylphorbol Acetate

Most allergic reactions are induced by mast cell activation. Mast cells play vital roles in the pathogenesis of allergic diseases. Bisdemethoxycurcumin (BDMC), a natural curcuminoid, has potential anti-allergic effects. Hence, we explored the effect of BDMC on mast cell-mediated allergic diseases. The study proved that BDMC suppresses β-hexosaminidase release, granule release, and membrane ruffling in monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA)-stimulated rat basophilic leukaemia cells (RBL-2H3 cells), and BDMC suppressed ovalbumin (OVA)-induced allergic rhinitis (AR) symptoms and OVA-specific IgE levels in AR mice. Furthermore, BDMC increased the survival of compound 48/80 anaphylaxis shock mice and elevated the decreased rectal temperature in OVA-induced active systemic anaphylaxis mice. These findings indicate that BDMC regulates the degranulation of mast cells, demonstrating its potential in the treatment of mast cell-induced allergic reactions.

Topics: Anaphylaxis; Animals; Cell Line; Curcumin; Diarylheptanoids; Hypersensitivity; Male; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; p-Methoxy-N-methylphenethylamine; Rats; Rhinitis, Allergic

We herein examined the importance of H2-Eb1 and H2-Ab1 in the susceptibility of mice to allergic rhinitis (AR) by developing double-gene (H2-Eb1+H2-Ab1) knockout mice. The mice were randomly grouped into different sensitization and excitation treatments, then their behavioral scores; nasal mucosa HE staining; thymus tissue toluidine blue staining; levels of ovalbumin (OVA)-specific IgE, IL-2 and IL-13 in the serum; and expression of IL-2 and IL-13 in the nasal mucosa were observed. H2-Ab1 and H2-Eb1 were both successfully knocked out in the study group (KO-OVA). Compared with the control group (WT-OVA), the nasal mucosal tissue in the KO-OVA mice showed fewer histological changes, reduced numbers of eosinophilic granulocytes, fewer mast cells in the thymus tissue, reduced concentrations of OVA-specific IgE and IL-13 in the serum, and reduced expression of IL-13 in the nasal mucosa. The behavior of the mice was also improved. In addition, the IL-2 concentration in the serum and IL-2 expression in the nasal mucosa were increased. There were two important findings of this study: (1) The H2-Ab1 and H2-Eb1 double knockout model of allergic rhinitis was successfully constructed, and the Th1/Th2 cell factors were in imbalance in these mice compared to WT mice; (2) the AR susceptibility of the dual knockout mice was reduced, confirming that H2-Ab1 and H2-Eb1 contribute to allergic rhinitis, at least in mice.

Topics: Animals; Disease Models, Animal; Eosinophils; Female; Histocompatibility Antigens Class II; Immunoglobulin E; Interleukin-13; Interleukin-2; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Knockout; Nasal Mucosa; Ovalbumin; Random Allocation; Rhinitis, Allergic

Coptisine is one of the main components of isoquinoline alkaloids in the coptidis rhizome. The effect of coptisine on allergic rhinitis has not been investigated. In this study, we report the effects and mechanisms of coptisine using monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA)-stimulated rat basophilic leukemia cells (RBL-2H3 cells) in vitro and an ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. The results showed that coptisine markedly decreased the levels of β-hexosaminidase, histamine, interleukin (IL)-4, and tumor necrosis factor (TNF)-α. Coptisine also prevented morphological changes, such as restoring an elongated shape, inhibiting granule release on toluidine blue staining, and reorganizing inhibited filamentous actins (F-actin). Additionally, coptisine blocked the phosphorylation of phosphoinositide3-kinase (PI3K)/Akt (as known as protein kinase B(PKB)) in RBL-2H3 cell. Furthermore, the results showed that coptisine suppressed OVA-induced allergic rhinitis symptoms, such as nasal rubbing and OVA-specific IgE, and histamine, IL-4 and TNF-

Topics: Animals; Berberine; beta-N-Acetylhexosaminidases; Cell Degranulation; Cell Line; Disease Models, Animal; Histamine; Immunoglobulin E; Interleukin-4; Mast Cells; Mice; Ovalbumin; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rhinitis, Allergic; Tumor Necrosis Factor-alpha

Exposure to fine particulate matter (particulate matter ≤2.5 μm [PM2.5]) increases the risk of allergic rhinitis (AR), but the underlying mechanisms remains unclear. Thus, we investigated the roles of T-helper (Th)1-Th2 cytokines and nasal remodeling after ambient PM2.5 exposure in a rat model of AR.. Female Sprague-Dawley rats were randomized into six groups: a negative control group, a group of healthy rats exposed to 3000 μg/m3 PM2.5, an ovalbumin (OVA) induced AR model, and three PM2.5-exacerbated AR groups exposed to three different concentrations (200, 1000, and 3000 μg/m3) of PM2.5 for 30 days via inhalation. Nasal symptoms, levels of Th1-Th2 cytokines, the degree of eosinophilia in nasal lavage fluid (NLF), and the messenger RNA (mRNA) expressions of transcription factors GATA-3 and T-bet in the nasal mucosa were measured in each individual rat. Hyperplasia of globet cells and collagen deposition were examined by histology.. PM2.5 significantly increased the number of sneezes and nasal rubs in rats with AR. PM2.5 also significantly decreased interferon gamma and increased interleukin (IL) 4 and IL-13 expressions as well as the number of eosinophils in NLF. The mRNA expression of GATA-3 in the nasal mucosa of rats with AR was upregulated by PM2.5, whereas T-bet was significantly downregulated. Statistically significant differences in OVA-specific serum immunoglobulin E, goblet cell hyperplasia, collagen deposition, and transforming growth factor beta 1 levels were observed between the PM2.5-exacerbated AR groups and the AR model group.. Analysis of our data indicated that an increase in the immune response with Th2 polarization and the development of nasal remodeling may be the immunotoxic mechanisms behind the exacerbation of AR after exposure to PM2.5.

Topics: Allergens; Animals; Cytokines; Disease Models, Animal; Environmental Exposure; Eosinophils; Female; GATA3 Transcription Factor; Gene Expression Regulation; Humans; Hyperplasia; Immunoglobulin E; Nasal Mucosa; Ovalbumin; Particulate Matter; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Th1 Cells; Th1-Th2 Balance; Th2 Cells

We aimed to investigate whether quercetin had a therapeutic effect in an experimental rat model of allergic rhinitis. The study was conducted with 35 rats, which were randomly assigned into 4 groups: group 1 (n = 5), sham group; group 2 (quercetin group, n = 10) received 80 mg/kg day quercetin; group 3 (steroid group, n = 10) received steroid (mometasone furoate); and group 4 (control group, n = 10), received ovalbumin alone. Rats were sensitized by administration of ovalbumin on alternate days over 14 days via an intraperitoneal route. On day 15, in addition to ovalbumin via an intranasal route, quercetin and steroid were given over 7 days to the corresponding groups. All rats were then sacrificed and nasal turbinates were evaluated histopathologically, and serum total IgE and ovalbumin (OVA)-specific IgE values were measured before and after treatment. A significant increase in OVA-specific IgE values was detected in all groups except sham group. A significant increase was detected in post-treatment total IgE levels in the control group, while no significant change was detected in the sham, quercetin, and intranasal steroid groups. On histopathological evaluation, it was observed that findings of allergic rhinitis were suppressed in the quercetin group when compared to the control group. In immunohistochemical evaluation, it was detected that COX-2 and VIP expressions were weaker in the quercetin group compared to the control group. Based on these findings, we conclude that quercetin was effective in allergic rhinitis induced by ovalbumin in rats both histopathologically and serologically.

Topics: Administration, Intranasal; Animals; Anti-Allergic Agents; Antioxidants; Cyclooxygenase 2; Disease Models, Animal; Immunoglobulin E; Mometasone Furoate; Ovalbumin; Quercetin; Random Allocation; Rats; Rhinitis, Allergic; Turbinates

Glucosamine (GlcN) is generally used as a dietary supplement because of its antiinflammatory effects. We evaluated the antiallergic effect of GlcN in mice with allergic asthma and rhinitis.. Thirty-two mice were allocated equally into 4 groups (n = 8). In group A (control), we performed intraperitoneal/intranasal challenge using sterile saline. In group B (asthma/rhinitis), we used ovalbumin for intraperitoneal/intranasal challenge to induce allergic asthma and rhinitis. In groups C and D (GlcN treatment), mice were given 1% and 5% GlcN throughout the period of ovalbumin challenge, respectively. We measured serum total and ovalbumin-specific immunoglobulin E (IgE), cytokine titers (interleukin-1, -4, -5, -6, -10, and -17; tumor necrosis factor-α; and interferon-γ), and the number of inflammatory cells (eosinophils, neutrophils, lymphocytes) in bronchoalveolar lavage (BAL) fluid. We also performed histopathologic examination of the lung and nasal cavity. Finally, we performed real-time polymerase chain reaction for the genes Bcl-2, EC-SOD, VEGF, caspase-3, Bax, COX-2, Hif-1α, and heme oxygenase-1.. Compared with group B, group D had significant serum total and ovalbumin-specific IgE decreases after GlcN treatment (p < 0.05). Titers for IL-4, IL-5, IL-6, and IL-17 in BAL fluid were significantly decreased in group D (p < 0.05). Eosinophils in BAL fluid were significantly decreased in group D compared with group B (p < 0.05). Groups C and D showed significant improvement of inflammation compared with group B. Group D had significant downregulation of EC-SOD, Bax, Hif-1α, and heme oxygenase-1 compared with group B.. GlcN had a significant antiallergic effect in mice with allergic asthma and rhinitis.

Topics: Allergens; Animals; Anti-Allergic Agents; Asthma; bcl-2-Associated X Protein; Bronchoalveolar Lavage Fluid; Cytokines; Female; Gene Expression Regulation; Glucosamine; Heme Oxygenase-1; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoglobulin E; Leukocyte Count; Lung; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Superoxide Dismutase

Currently, a variety of studies have demonstrated that green tea has anti-allergic properties, and the major polyphenolic compound, epigallocatechin gallate (EGCG), plays a significant role. Some research indicates that EGCG reduces the production and expression of allergy-related substances. Therefore, EGCG has a potential effect of reducing allergic rhinitis (AR). In this study, the effect of EGCG on allergic rhinitis in an ovalbumin (OVA)-induced mouse model was investigated. After administration of EGCG, the number of sneezes and the occurrence of nasal rubbing were significantly decreased, the concentrations of immunoglobulin E (IgE) and histamine were suppressed in AR mouse serum, the levels of interleukin (IL)-1β, IL-4, and IL-6 were reduced in AR mice nasal lavage fluid (NLF), and the nasal mucosa mRNA and protein expression of cyclooxygenase 2 (COX-2), IL-1β, IL-4, and IL-6 were inhibited. The data indicate that EGCG has a beneficial effect of reducing allergic rhinitis.

Topics: Allergens; Animals; Anti-Inflammatory Agents; Catechin; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Female; Histamine; Humans; Immunoglobulin E; Inflammation Mediators; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Sneezing; Tea

This study aimed to investigate the effect of blocking Notch signaling by γ-secretase inhibitor (GSI) on allergic rhinitis.. GSI, N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butylester (DAPT) was administered to ovalbumin-induced AR mice models intranasally. We observed symptoms of sneezing and nose rubbing. To detect the inflammatory state, the serum OVA-specific-IgE, IFN-γ, IL-4, and IL-5 were analyzed by ELISA, and Th cell cytokines in nasal mucosa were analyzed by RT-PCR, including T-bet, IFN-γ, GATA-3, IL-4, and IL-5. In addition, hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) were applied for histopathological examination. As for the evaluation of Notch signaling, we analyzed the Notch-1, Notch signaling target Hes-1, and Hes-5 in mucosa by RT-PCR, besides, used western blotting and immunohistochemistry to assess NICD (Notch intracellular domain).. The results showed that the DAPT ameliorated the development of AR and suppressed Th2 cytokine levels significantly, alleviating eosinophils infiltration and goblet cells metaplasia, suggesting that the GSI can regulate Th2 response and weaken airway inflammation in AR.. Our findings provide evidence that blocking Notch signaling by GSI offers high value in treating AR.

Topics: Administration, Intranasal; Amyloid Precursor Protein Secretases; Animals; Blotting, Western; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Real-Time Polymerase Chain Reaction; Rhinitis, Allergic; Signal Transduction; Th1 Cells

3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosyl-cycloastragenol, or Astragaloside IV (AST), is one of the major active ingredients isolated from Astragalus membranaceous with distinct pharmacological effects, and possesses anti-inflammatory, immunoregulatory and antifibrotic properties. However, the effects of AST on allergic rhinitis remain to be elucidated. The present study aimed to examine the effects of AST on immunoglobulin (Ig) E‑mediated allergic reactions in vivo, by using a mouse model of allergic rhinitis established via repetitive sensitization and intranasal challenge with ovalbumin (OVA). Intragastric administration of AST (25 mg/kg or 50 mg/kg) or dexamethasone (DEX; 3 mg/kg) significantly alleviated the inflammatory response, nasal symptoms and mucosa remodeling, and decreased the serum levels of OVA‑specific IgE in allergic mice. Furthermore, treatment with AST or DEX significantly suppressed the mRNA and protein expression levels of the transcription factor GATA‑3 and retinoic acid receptor‑related orphan nuclear receptor (ROR)γt in tissue samples isolated from the spleen and nasal mucosa of mice with allergic rhinitis. Conversely, mRNA and protein expression levels of T‑box protein expressed in T cells (T‑bet) and forkhead box protein 3 (Foxp3) were upregulated in the spleen and nasal mucosa of mice with allergic rhinitis following treatment with AST or DEX, and spleen protein levels of signal transducer and activator of transcription 3 followed a similar trend. In addition, treatment with AST was associated with fewer adverse events compared with treatment with DEX. The present results suggested that treatment with AST may attenuate OVA‑induced allergic rhinitis via regulating the expression of the transcription factors GATA‑3, RORγt, T‑bet and Foxp3, which commit T helper cells to the Th1 phenotype. Therefore, AST may represent an alternative therapeutic approach for the treatment of patients with allergic rhinitis.

Topics: Allergens; Animals; Biomarkers; Dexamethasone; Disease Models, Animal; DNA-Binding Proteins; Female; GATA3 Transcription Factor; Gene Expression Regulation; Immunoglobulin E; Male; Mice; Nasal Mucosa; Nerve Tissue Proteins; Nuclear Proteins; Nuclear Receptor Subfamily 1, Group F, Member 3; Ovalbumin; Protective Agents; Rhinitis, Allergic; RNA, Messenger; Saponins; Spleen; T-Box Domain Proteins; T-Lymphocyte Subsets; Triterpenes

Taurine has been widely evaluated as a potential therapeutic agent in chronic inflammatory disorders and various infections. However, the potential role of taurine in regulating allergic inflammatory responses is currently unknown.. The present study was designed to evaluate the in vitro effects of taurine on the levels of thymic stromal lymphopoietin (TSLP) and other pro-inflammatory cytokines and activation of caspase-1 and nuclear factor (NF)-κB as well as the phosphorylations of c-Jun N-terminal kinase (JNK) and p38 in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-triggered human mast cell line, HMC-1 cells. Furthermore, we assessed the therapeutic effects of taurine on ovalbumin (OVA)-induced allergic rhinitis (AR) animal models.. Here, the obtained results showed that taurine dose-dependently inhibited the production and mRNA expression of TSLP and pro-inflammatory cytokines in HMC-1 cells exposed to PMACI. Taurine attenuated the phosphorylation of JNK and p38 in activated HMC-1 cells. Moreover, taurine brought a significant inhibition of the activities of NF-κB and caspase-1. In an OVA-induced AR animal model, the increased levels of nose rubbing, histamine, immunoglobulin E, TSLP, and interleukin IL-1β were dramatically reduced by the administration of taurine. In summary, taurine could serve as potential novel remedy of allergic inflammatory disorders.

Topics: Animals; Caspase 1; Cell Line; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Histamine; Humans; Immunoglobulin E; Inflammation; Inflammation Mediators; JNK Mitogen-Activated Protein Kinases; Mast Cells; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Taurine; Thymic Stromal Lymphopoietin

Oxidative stress is involved in various diseases, including allergies. Several studies have pointed to the preventive and therapeutic potential of antioxidants in allergic disorders. However, little is known about the immunomodulatory effects of antioxidants in type I hypersensitivity. In this study we aimed to explore the impact of a water-soluble antioxidant and α-lipoic acid derivative, sodium zinc histidine dithiooctanamide (DHL-HisZn), on mast-cell- and T-cell-mediated allergic and immune responses both in vitro and in vivo.. The therapeutic impact of DHL-HisZn on mast-cell-mediated type I hypersensitivity was evaluated by a mast-cell degranulation assay using bone marrow-derived mast cells and by a mouse model of ovalbumin (OVA)-induced allergic rhinitis. The effect of DHL-HisZn on the proportion of regulatory T cells (Tregs) was evaluated using flow cytometry.. During the course of OVA-induced allergic rhinitis in mice, serum nitrate was elevated, suggesting the involvement of oxidative stress in allergic responses. DHL-HisZn not only suppressed mast-cell degranulation but also ameliorated OVA-induced nasal hypersensitivity, with significant suppression of serum nitrate. DHL-HisZn treatment significantly suppressed OVA-specific immunoglobulin E (IgE) but enhanced OVA-specific IgG2a in OVA-sensitized and nasal-challenged mice. Furthermore, DHL-HisZn treatment suppressed interleukin-17 production in OVA-stimulated splenocytes. Finally, we demonstrated the induction of Tregs by DHL-HisZn in concanavalin A blasts.. These findings suggest that DHL-HisZn may regulate mast-cell-, T-helper 2 (Th2)-, and Th17-mediated allergic and immune responses by induction of Tregs.

Topics: Allergens; Alum Compounds; Animals; Antioxidants; Cell Degranulation; Cytokines; Disease Models, Animal; Female; Histidine; Immunoglobulin E; Immunoglobulin G; Male; Mast Cells; Mice, Inbred BALB C; Ovalbumin; Rats, Inbred Lew; Rhinitis, Allergic; Spleen; T-Lymphocytes, Regulatory; Thioctic Acid

Allergic rhinitis is a common heterogeneous chronic upper airway disorder and is an IgE-mediated inflammation characterized by one or more nasal symptoms such as sneezing, itching, nasal discharge, rhinorrhea, post nasal drainage and nasal blockage. In the present study, the effects of skullcapflavone II (SCFII) on upper airway inflammation, Th2 cytokines, and NF-κB signaling in an ovalbumin (OVA)-induced allergic rhinitis (AR) murine model in vivo were investigated. OVA-induced AR mice increased nasal symptoms, eosinophils and mast cells infiltration into nasal cavity, OVA-specific IgE/IgG1 and histamine in serum, Th2 cytokines including IL-13 and GATA3, and NF-κB signaling in NALF and lung homogenate. Interestingly, treatment of SCFII reduced the levels of OVA-specific IgE/IgG1 and histamine in serum, of Th2 cytokines and of NF-κB signaling in the NALF and the lung homogenate, and histopathological changes in the nasal tissue and the lung. Also, dexamethasone suppressed such increases. The results of this study suggested that SCFII may ameliorate allergic inflammation of upper airway in AR mice model by blocking the Th2 cytokine production, the NF-κB signal pathway and the mast cell histamine release. Taken together, we suggest that SCFII may be used as a therapeutic agent for patients with Th2-mediated or mast cell-mediated allergic diseases.

Topics: Allergens; Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Flavonoids; Histamine; Humans; Immunoglobulin E; Male; Mast Cells; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Th2 Cells

Anticholinergic agent, ipratropium bromide (IB) ameliorates symptoms of allergic rhinitis (AR) using neuroimmunologic mechanisms. However, the underlying molecular mechanism remains largely unclear. In the present study, 27 mice with AR induced by ovalbumin were randomly allocated to one of three groups: Model group, model group with IB treatment for 2 weeks, and model group with IB treatment for 4 weeks. Allergic symptoms were evaluated according to symptoms scores. Differentially expressed genes [microRNAs (miRNAs) and messenger RNAs (mRNAs)] of nasal mucosa were identified by microarray analysis. The expression levels of candidate genes were measured by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The data indicates that the symptoms scores in allergic mice were significantly reduced by IB treatment. In the nasal mucosa of allergic mice with IB treatment, 207 mRNAs and 87 miRNAs were differentially expressed, when compared with the sham group. IB treatment significantly downregulated the expression levels of interleukin‑4Rα and prostaglandin D2 synthase, whereas the leukemia inhibitory factor, A20 and nuclear receptor subfamily 4, group A, member 1 expression levels were upregulated. Similarly, the expression levels of mmu‑miR‑124‑3p/5p, ‑133b‑5p, ‑133a‑3p/5p, ‑384‑3p, ‑181a‑5p, ‑378a‑5p and ‑3071‑5p were significantly increased. RT‑qPCR data further validated these mRNA and miRNA expression levels. Thus, IB treatment regulated expression of allergic immune‑associated mRNAs and miRNAs of the nasal mucosa in allergic mice, which may be associated with ameliorated nasal allergic symptoms.

Topics: Animals; Cholinergic Antagonists; Disease Models, Animal; Down-Regulation; Male; Mice; Mice, Inbred BALB C; MicroRNAs; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; RNA, Messenger; Transcriptome

Food allergy is immediate hypersensitive reactions to ingested foods. Since early diagnosis is effective for disease control, development of an objective diagnostic index is required. Using mediator-lipidomics, we found that levels of the urinary prostaglandin D

Topics: Animals; Asthma; Dermatitis, Atopic; Food Hypersensitivity; Humans; Hyperplasia; Intestines; Intramolecular Oxidoreductases; Lipocalins; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Prostaglandin D2; Rhinitis, Allergic

Allergen-mediated cross-linking of IgE on mast cells/basophils is a well-recognized trigger for type 1 allergic diseases such as allergic rhinitis (AR). However, allergens may not be the sole trigger for AR, and several allergic-like reactions are induced by non-IgE-mediated mechanisms.. We sought to describe a novel non-IgE-mediated, endotoxin-triggered nasal type-1-hypersensitivity-like reaction in mice.. To investigate whether endotoxin affects sneezing responses, mice were intraperitoneally immunized with ovalbumin (OVA), then nasally challenged with endotoxin-free or endotoxin-containing OVA. To investigate the role of T cells and mechanisms of the endotoxin-induced response, mice were adoptively transferred with in vitro-differentiated OVA-specific T

Topics: Allergens; Animals; Endotoxins; Histamine; Immunoglobulin E; Mice, Inbred BALB C; Mice, Knockout; Myeloid Differentiation Factor 88; Nasal Mucosa; Ovalbumin; Respiratory Hypersensitivity; Rhinitis, Allergic; T-Lymphocytes; Toll-Like Receptor 4

Previous studies showed that bone marrow-derived mesenchymal stem cells (BMSCs) could ameliorate a variety of immune-mediated and inflammatory diseases due to their immunomodulatory and anti-inflammatory effects. In this study, we developed a mouse model of ovalbumin (OVA) induced allergic inflammation in the upper airways and evaluated the effects of the intraperitoneal administration of BMSCs on allergic inflammation. Twenty-five BALB/c mice were divided into five groups; group I (control group), group II (sensitized and challenged with OVA and treated with saline-placebo group), group III (sensitized and challenged with OVA and treated with 1 × 10

Topics: Allergens; Animals; Biomarkers; Cytokines; Enzyme-Linked Immunosorbent Assay; Injections, Intraperitoneal; Male; Mesenchymal Stem Cell Transplantation; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Random Allocation; Rhinitis, Allergic

The proinflammatory cytokine interleukin (IL)-17A is associated with eosinophil infiltration into the nasal mucosa in a mouse model of ovalbumin-induced allergic rhinitis. Chemotaxis of eosinophils is mediated primarily through C-C chemokine receptor type 3 (CCR3). However, the mechanism underlying the IL-17A-mediated enhancement of eosinophil recruitment via chemoattractants/chemokines remains unknown.. In this study, we assessed the contribution of IL-17A to eosinophil-related inflammation via the CCL7/CCR3 pathway in experimental allergic rhinitis.. IL-17A knockout (KO) and wild-type (WT) BALB/c mice were injected intraperitoneally and challenged intranasally with OVA to induce allergic rhinitis. Various parameters of the allergic response were evaluated, and mRNA and protein levels of CCL7 and CCR3 in nasal tissue and serum were compared between the two groups. The chemotactic response to CCL7 with or without IL-17A in bone marrow-derived eosinophils (bmEos) from BALB/c mice was measured.. In the allergic rhinitis model, IL-17A deficiency significantly decreased nasal symptoms, serum IgE levels, and eosinophil recruitment to the nasal mucosa. CCL7 and CCR3 mRNA and protein levels were decreased in the nasal mucosa of IL-17A KO mice compared with the WT mice. BmEos showed a significantly increased chemotactic response to -low concentration of CCL7 in the presence of IL-17A compared with its absence.. The suppression of nasal inflammation due of IL-17A deficiency in allergic rhinitis is partly responsible for the regulation of CCL7 secretion and eosinophil infiltration, which may be regulated via the CCL7/CCR3 pathway.

Topics: Animals; Bone Marrow Cells; Chemokine CCL7; Chemotaxis; Disease Models, Animal; Eosinophils; Female; Immunoglobulin E; Interleukin-17; Mice, Inbred BALB C; Mice, Knockout; Nasal Mucosa; Ovalbumin; Receptors, CCR3; Rhinitis, Allergic; RNA, Messenger

A novel independent Th-cell subset, characterized by high expression of interleukin (IL)-9, has been recognized as the "Th9" subset. Although Th9 cells are important in many diseases, their contribution to allergic rhinitis (AR) remains unclear. We therefore first determined whether Th9 cells were present in a mouse model of AR. We then investigated the their involvement in the distribution of CD4+ T-cell subsets and the symptoms of AR by treating mice with anti-IL-9 antibodies (Abs). Anti-IL-9 Abs were administered intranasally during rechallenge of ovalbumin (OVA)-induced AR in BALB/c mice. We measured nasal rubbing motion, sneezing and eosinophils, as well as the Th1 (Th1 cell percentage, Ifn-γ mRNA/protein, T-bet mRNA), Th2 (Th2 cell percentage, Il-4 mRNA/protein, Gata3 mRNA), Th9 (Th9 cell percentages Il-9 mRNA/protein, PU.1 and Irf4 mRNA), Th17 (Th17 cell percentage, Il-17 mRNA/protein, Rorγt mRNA), and Treg (Treg cell percentage, Foxp3 mRNA) responses in the nasal mucosa. Treatment with anti-IL-9 Abs markedly reduced nasal rubbing, sneezing, eosinophil infiltration, and Th2, Th9, and Th17 responses, and increased the Treg response. Our findings emphasize the importance of IL-9/Th9 in the pathogenesis of AR, and suggest that anti-IL-9 Ab treatment may be an effective therapeutic strategy for AR.

Topics: Animals; Antibodies, Neutralizing; CD4-Positive T-Lymphocytes; Cells, Cultured; Cytokines; Disease Models, Animal; Eosinophils; Female; Interleukin-9; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; T-Lymphocytes, Regulatory; Th17 Cells; Th2 Cells

To investigate the effects of Yupingfeng granule (YPF) on immune factors of the rats with allergic rhinitis (AR) induced by ovalbumin(OVA). OVA 0.3 mg, Al(OH)3 30 mg and saline 1 mL were mixed and intraperitoneally injected for the initial immunization, 4% OVA 200 μg (50 μL) was given to the nose on the 15th day for the second immunization to establish the allergic rhinitis model. Sixty male SD rats were randomly divided into allergic rhinitis(AR) model group, Yupingfeng granule three dose (2.7,1.35,0.68 g•kg⁻¹) groups, control drug Biyankang (0.4 g•kg⁻¹) and normal control group. After 14 days, efforts were made to collect blood from abdominal aorta, and take nasopharynx tissues and fasten them into 10% formaldehyde for a pathological examination. The levels of HIS, IgE, IL-4 and TNF-α in serum were examined by radioimmunoassay, and nasal mucosa tissues were examined by HE staining. According to the results, the levels of HIS, IgE, IL-4 and TNF-α in serum of Yupingfeng granule groups were significantly lower than that of AR model group (P<0.05, P<0.01). Nasal mucosa tissues showed slight morphological changes and inflammatory cell infiltration, with unobvious necrosis. Yupingfeng granule can improve the pathological changes of nasal mucosa tissues, and reduce the production and release of immune factors during allergic rhinitis (AR) process in vivo by OVA, which may be the important curative mechanism of allergic rhinitis.

Topics: Animals; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Humans; Male; Nasal Mucosa; Ovalbumin; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Tumor Necrosis Factor-alpha

Topics: Animals; Disease Models, Animal; Interferon-gamma; MAP Kinase Kinase 4; Nasal Mucosa; Ovalbumin; Phosphorylation; Rats; Rats, Wistar; Rhinitis, Allergic

Allergic rhinitis (AR) is an allergic inflammation of the nasal airways. The Korean herbal medicine, So-Cheong-Ryong-Tang (SCRT) has been typically used for the treatment of AR for hundreds of years. In the present study, we investigated whether SCRT suppresses the progression of AR in animal model. AR was induced by ovalbumin (OVA). Treatment with SCRT was assessed to study the effect of SCRT on AR in mice. Histological analysis, multiplex cytokine assay, blood analysis, cell viability assay, RT-PCR and Elisa assay were performed to verify inhibitory effect of SCRT on AR. SCRT reduced infiltration of inflammatory cells into nasal cavity. SCRT reduced infiltration of mast cells into nasal mucosa. SCRT reduced the levels of cytokines (IL-4 and LIF) in the serum. SCRT reduced the levels of leukocytes in the blood. SCRT decreased cell viability of HMC-1 cells and splenocyte. SCRT suppressed IL-4 level in HMC-1 cells and splenocyte cells in a dose-dependent manner. SCRT suppressed IL-6 level and TNF-α level in splenocyte. SCRT suppresses the progression of AR induced by OVA. SCRT might be a useful drug for the treatment of AR.

Topics: Animals; Anti-Allergic Agents; Cell Survival; Disease Models, Animal; Drugs, Chinese Herbal; Interleukin-4; Interleukin-6; Leukemia Inhibitory Factor; Leukocytes; Mast Cells; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Phytotherapy; Rhinitis, Allergic; Spleen; Tumor Necrosis Factor-alpha

To determine whether intranasal infusion of botulinum toxin type A (BTX-A) relieves symptoms of ovalbumin (OVA)-induced allergic rhinitis (AR) and reduces nasal inflammation in mice.. AR was induced via intraperitoneal injection of OVA followed by daily intranasal challenge with OVA. Five weeks after the initiation of OVA sensitization, nasal cavities were exposed to a single intranasal infusion of BTX-A. The behavior of mice was observed before and 1, 3, 5, 7, 14, 21, and 28days after infusion. Mice were sacrificed after 28days and late histological findings were examined. PBS was administered to control mice.. On Day 3, the frequency of typical AR symptoms, including sneezing and nose scratching, significantly decreased in the BTX-A-treated group (n=6) compared to the control group (n=6). Although the AR-inhibiting effects of BTX-A persisted until Day 21, AR symptoms re-appeared in response to daily OVA stimulation. Histological findings of the nasal mucosa also improved following BTX-A administration. Although capillary dilatation and eosinophil infiltration decreased by Day 3, these effects disappeared by Day 28. In contrast, the number and size of the secretary glands in the nasal mucosa did not change following BTX-A administration. PBS had no effect on nasal symptoms or histology.. Topical treatment with BTX-A efficiently and temporarily ameliorates AR symptoms. Intranasal infusion does not cause pain or bleeding, and the effects of a single infusion of BTX-A last for at least three weeks. This treatment might be a promising therapeutic strategy for the treatment of AR.

Topics: Administration, Intranasal; Animals; Behavior, Animal; Botulinum Toxins, Type A; Delayed-Action Preparations; Disease Models, Animal; Eosinophils; Female; Inflammation; Mice; Nasal Mucosa; Neurotoxins; Ovalbumin; Rhinitis, Allergic; Time Factors

The underlying mechanisms of mesenchymal stromal cells (MSCs) on immune modulation to treat allergic diseases remain unclear. Here, we showed that the suppressor of cytokine signaling 3 (SOCS3) is an important immune modulator expressed by MSCs, which is significantly increased by interferon-γ (IFN-γ). In addition, we observed that SOCS3 is a crucial mediator of the anti-proliferative and functional effects of MSCs on T cells and B cells. The immune modulation of MSCs through SOCS3 is mediated by cell-cell contacts. Moreover, SOCS3 could serve as an indicator to predict the potential immune modulatory of MSCs derived from different donors. Furthermore, treatment with anti-SOCS3 Ab significantly decreased ovalbumin-specific antibodies and neutrophil infiltration in ovalbumin-induced allergic rhinitis (AR) mice. Our results suggest that SOCS3 serves as an immune modulator interfering with T cells and B cells, and SOCS3 may act as a predictive marker for immune modulatory of MSCs.

Topics: Animals; B-Lymphocytes; Cell Proliferation; Cells, Cultured; Female; Humans; Immunoglobulin E; Immunomodulation; Interferon-gamma; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Neutrophil Infiltration; Ovalbumin; Rhinitis, Allergic; Suppressor of Cytokine Signaling 3 Protein

Allergic rhinitis (AR) is one of the common disorders in airway allergic inflammation. The pathogenesis of AR is unclear. It is accepted that immune deregulation is associated with the pathogenesis of AR. Recent reports suggest that a large number of micro RNAs (miR) can regulate immune functions. This study aims to investigate the role of miR-146a in an enforcing immunotherapy of AR. In this study, a mouse AR model was created. The levels of miR-146a in the mouse nasal mucosa were assessed by real time RT-PCR. A specific immunotherapy was performed in AR mice. The results showed that the AR mice had an AR-like inflammation in the nasal mucosa. Compared with naïve mice, markedly lower levels of miR-146a were detected in AR mice. The co-administration with miR-146a significantly enforced the effect of ovalbumin (OVA)-specific immunotherapy on inhibition of AR inflammation in the nasal mucosa. Further analysis showed that miR-146a induced transforming growth factor-β in dendritic cells; the latter induced naïve CD4(+) T cells to differentiate into regulatory T cells. In conclusion, miR-146a can enforce OVA-specific immunotherapy via inducing antigen-specific regulatory T cells. miR-146a may have therapeutic potential to be used in the immunotherapy of allergic diseases.

Topics: Animals; Case-Control Studies; Cytokines; Dendritic Cells; Disease Models, Animal; Epitopes, T-Lymphocyte; Gene Expression; Humans; Immunoglobulin E; Immunotherapy; Immunotherapy, Adoptive; Lymphocyte Count; Male; Mice; MicroRNAs; Nanoparticles; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; T-Cell Antigen Receptor Specificity; T-Lymphocyte Subsets; Transforming Growth Factor beta; Vaccines

Transient receptor potential vanilloid 1 (TRPV1), which has been identified as a molecular target for the activation of sensory neurons by various painful stimuli, was reported to regulate the signaling and activation of CD4+ T cells. However, the role of TRPV1 in CD4+ T cell in allergic rhinitis remains poorly understood. In this study, TRPV1 expression was localized in CD4+ T cells. Both knockout and chemical inhibition of TRPV1 suppressed Th2/Th17 cytokine production in CD4 T cells and Jurkat T cells, respectively, and can suppress T cell receptor signaling pathways including NF-κB, MAP kinase, and NFAT. In TRPV1 knockout allergic rhinitis (AR) mice, eosinophil infiltration, Th2/Th17 cytokines in the nasal mucosa, and total and ova-specific IgE levels in serum decreased, compared with wild-type AR mice. The TRPV1 antagonists, BCTC or theobromine, showed similar inhibitory immunologic effects on AR mice models. In addition, the number of TRPV1+/CD4+ inflammatory cells increased in the nasal mucosa of patients with AR, compared with that of control subjects. Thus, TRPV1 activation on CD4+ T cells is involved in T cell receptor signaling, and it could be a novel therapeutic target in AR.

Topics: Adolescent; Adult; Animals; Blotting, Western; CD4-Positive T-Lymphocytes; Cytokines; Eosinophils; Female; Humans; Immunoglobulin E; Immunohistochemistry; Inflammation; Jurkat Cells; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Nasal Mucosa; Ovalbumin; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis, Allergic; TRPV Cation Channels; Young Adult

Bacterial flagellin, a Toll-like receptor 5 agonist, is used as an adjuvant for immunomodulation. In this study, we aimed to evaluate the effect and its mechanism following intralymphatic administration of OVA-flagellin (FlaB) mixture in the mouse model of allergic rhinitis.. BALB/c mice were sensitized with OVA and treated with an OVA-FlaB mixture via intranasal, sublingual, and intralymphatic routes to evaluate the effect of each treatment. Several parameters for allergic inflammation and its underlying mechanisms were then evaluated.. Intralymphatic injection of the OVA-FlaB mixture reduced symptom scores, eosinophil infiltration in the nasal mucosa, and total and OVA-specific IgE levels more significantly than intranasal and sublingual administration. Systemic cytokine (IL-4, IL-5, IL-6, IL-17, and IFN-γ) production and local cytokine (IL-4 and IL-5) production were also reduced significantly after intralymphatic injection with OVA-FlaB. Double intralymphatic injection of the mixture was more effective than single injection. Moreover, the expression of innate cytokines such as IL-25 and IL-33 in nasal epithelial cells was reduced, and the expression of chemokines such as CCL24 (eotaxin-2), CXCL1, and CXCL2 was decreased in the nasal mucosa, suggesting the underlying mechanism for intralymphatic administration of the OVA-FlaB mixture.. Intralymphatic administration of an OVA-FlaB mixture was more effective in alleviating allergic inflammation than intranasal and sublingual administration in a mouse model of allergic rhinitis. This effect may be attributed to the reduced expression of innate cytokines and chemokines. This treatment modality can be considered as a new therapeutic method and agent.

Topics: Allergens; Animals; Antibody Specificity; Cytokines; Disease Models, Animal; Eosinophils; Female; Flagellin; Immunization; Immunoglobulin E; Immunohistochemistry; Mice; Nasal Mucosa; Neutrophil Infiltration; Ovalbumin; Rhinitis, Allergic; Severity of Illness Index; Spleen

Bamboo salt (BS) is a Korean traditional type of salt and has been reported to have therapeutic effects on allergic inflammation. Thymic stromal lymphopoietin (TSLP) aggravates inflammation in the pathogenesis of allergic reactions, such as allergic rhinitis (AR). To confirm an active compound of BS, we investigated the effect of sulfur, a compound of BS, on the levels of TSLP in a human mast cell line, HMC-1 cells and a mouse model of AR using hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaSH). We treated NaSH or BS in HMC-1 cells and activated the HMC-1 cells with phorbol myristate acetate and calcium ionophore A23187 (PMACI). ELISA for the production measurement of TSLP, PCR for the mRNA expression measurement of TSLP, and western blot analysis for the expression measurement of upstream mediators were performed. Mice were treated with NaSH and sensitized with ovalbumin (OVA). The levels of TSLP were measured in serum and nasal mucosa tissue in an OVA-induced AR mouse model. NaSH or BS diminished the production and mRNA expression of TSLP as well as interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the PMACI-activated HMC-1 cells. NaSH or BS diminished the level of intracellular calcium in the PMACI-activated HMC-1 cells. NaSH or BS reduced the expression and activity of caspase-1 in the PMACI-activated HMC-1 cells. And NaSH or BS inhibited the expression of receptor interacting protein-2 and the phosphorylation of extracellular signal-regulated kinase in the PMACI-activated HMC-1 cells. The translocation of NF-κB into the nucleus as well as the phosphorylation and degradation of IκBα in the cytoplasm were diminished by NaSH or BS in the PMACI-activated HMC-1 cells. Furthermore, NaSH inhibited the production of TSLP, IL-6, and IL-8 in TNF-α-activated HMC-1 cells. Finally, the administration of NaSH showed a decrease in number of rubs on mice with OVA-induced AR. And the levels of immunoglobulin E and TSLP in the serum and the level of TSLP in the nasal mucosa tissue of the OVA-induced AR mice were reduced by NaSH. In conclusion, these findings show that H2S, as an active compound of BS is a potential agent to cure allergic inflammation.

Topics: Active Transport, Cell Nucleus; Animals; Calcimycin; Calcium; Caspase 1; Cell Line; Cytokines; Extracellular Signal-Regulated MAP Kinases; Female; Humans; Hydrogen Sulfide; I-kappa B Proteins; Immunoglobulin E; Interleukin-6; Interleukin-8; Mast Cells; Medicine, Korean Traditional; Mice; Mice, Inbred BALB C; NF-kappa B; NF-KappaB Inhibitor alpha; Ovalbumin; Phosphorylation; Real-Time Polymerase Chain Reaction; Receptor-Interacting Protein Serine-Threonine Kinase 2; Rhinitis, Allergic; RNA, Messenger; Sulfides; Tetradecanoylphorbol Acetate; Thymic Stromal Lymphopoietin; Tumor Necrosis Factor-alpha

Gami-hyunggyeyeongyotang (GMHGYGT) is a polyherbal medicine derived from an oriental prescription traditionally used in the treatment of allergic diseases such as allergic rhinitis (AR). This study aimed to evaluate the effects of GMHGYGT on ovalbumin (OVA) sensitization/challenge-induced AR in BALB/C mice, through examination of allergic inflammatory response regulation, as well as examination of human mast cells (HMC-1).. Nasal symptoms were evaluated in the OVA-induced allergic rhinitis mouse model, and total immunoglobulin (Ig)E and OVA-specific IgE levels in serum were investigated. Eosinophil infiltration and thickness of the nasal mucosa, and levels of interleukin (IL)-1β and caspase-1 were also measured by immunohistochemistry. Additionally, the effect of GMHGYGT on the phorbol-12-myristate-13-acetate plus calcium ionophore A23187-induced phosphorylation of extracellular signal-regulated kinase, C-Jun N-terminal kinase and p38 in HMC-1 cells was investigated.. GMHGYGT was demonstrated to have antiallergic effects on the nasal symptoms of the OVA-induced mouse model, decreasing serum levels of OVA-specific IgE and levels of the cytokines IL-5, IL-6, IL-1β, monocyte chemotactic protein-1, and macrophage inflammatory protein-2. GMHGYGT reduced the number of eosinophils in the nasal mucosa and thickness of the nasal septum, and inhibited the expression of IL-1β and caspase-1. Moreover, it inhibited the phosphorylation of extracellular signal-regulated kinase and C-Jun N-terminal kinase, as well as the activation of nuclear factor-κB on protein level in HMC-1 cells.. These results suggest that GMHGYGT has therapeutic potential for the treatment of allergic rhinitis.

Topics: Animals; Anti-Allergic Agents; Cells, Cultured; Cytokines; Drugs, Chinese Herbal; Female; Humans; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-kappa B; Ovalbumin; Rhinitis, Allergic

Prostaglandin D2(PGD2) is involved in the pathogenesis of allergic rhinitis. However, the sensory nervous system-mediated contributions of PGD2to the symptoms of allergic rhinitis remain unclear. We investigated the involvement of PGD2in these symptoms and in neuronal excitation by in vivo and ex vivo experiments. In an ovalbumin-induced model of allergic rhinitis in guinea pigs, the number of sneezing, nasal rubbing, and nasal secretion events were assessed after the nasal cavity instillation of PGD2, histamine, or a combination of PGD2and histamine. In situ hybridization for PGD2receptor 1 (DP1) mRNA transcripts and immunohistochemical analysis of histamine H1receptor protein expression in guinea pig trigeminal ganglion (TRG) were performed. The effects of DP1receptor activation on the excitability of TRG neurons to electrical and histamine stimuli were assessed using whole-cell patch-clamp recordings. Histamine induced more sneezing, nasal rubbing, and nasal secretion events than PGD2 PGD2augmented histamine-induced responses, whereas pretreatment with a DP1receptor-selective antagonist completely suppressed PGD2-induced augmentation. DP1receptor mRNA transcripts and H1receptor protein expression could be detected in TRG neurons. Moreover, a DP1receptor agonist caused significant increases in the number of histamine-induced action potentials and depolarization, and reduced the current threshold in small-diameter neurons. Our findings show that PGD2-DP1receptor signaling augments the symptoms of allergic rhinitis via the sensory nervous system by modulating nasal neuronal activation to various stimuli, such as histamine. These findings suggest that DP1receptor antagonist has therapeutic potential for the treatment of allergic rhinitis.

Topics: Action Potentials; Animals; Behavior, Animal; Electric Stimulation; Guinea Pigs; Histamine; Male; Neurons; Ovalbumin; Patch-Clamp Techniques; Prostaglandin D2; Receptors, Immunologic; Receptors, Prostaglandin; Rhinitis, Allergic; Sneezing; Trigeminal Ganglion

Desloratadine is a biologically active metabolite of loratadine which is indicated for the treatment of allergic rhinitis. Bosentan is a dual endothelin receptor antagonist used to treatment of pulmonary artery hypertension (PAH). In this study, we aimed to determine the role of endothelins in allergic rhinitis (AR) and the effects of endothelin receptor antagonists in AR rat models through comparison with desloratadine.. In total, 20 adult Sprague-Dawley rats were used in this study. An ovalbumin-induced allergic rhinitis model was formed in three study groups except for the control group. Bosentan (100 mg/kg/day) was given to the bosentan-treated group for 7 days and desloratadine (10 mg/kg/day) was administered to the antihistaminic-treated group for 7 days. Nasal symptom scorings and histopathological examinations of the nasal tissues were carried out. Serum IgE levels and ET-1 and TNF-alpha mRNA expression levels were analysed. Between group comparisons for nasal symptoms, histopathological analysis, and molecular analyses were performed with a one-way ANOVA and Duncans multiple comparison tests. Significance was accepted at p smaller than 0.05.. Bosentan inhibited nasal symptom more significantly than desloratadine. The IgE level, ET-1 and TNF-alpha mRNA expression levels statistically increased in the allergic rhinitis group when compared to other groups. Conversely, the bosentan-treatment group showed a significant recovery from the same parameters. The deterioration in histopathological parameters reached the highest levels in the allergic rhinitis group. The histopathological findings were close to those of the control group in the bosentan and antihistaminic-treated group.. ET-1 is one of the mediators that impact AR development and ET-1 antagonists can be useful for symptom control and for decreasing allergic inflammation in AR patients.

Topics: Animals; Bosentan; Disease Models, Animal; Down-Regulation; Endothelin Receptor Antagonists; Endothelin-1; Female; Immunoglobulin E; Loratadine; Ovalbumin; Rats, Sprague-Dawley; Rhinitis, Allergic; RNA, Messenger; Sulfonamides; Tumor Necrosis Factor-alpha

Baicalin, a flavonoid compound purified from the dry roots of Scutellaria baicalensis Georgi, has generally been used for the treatment of various allergic diseases. However, there is little information about the anti-inflammatory effects of baicalin for allergic rhinitis. This study aims to investigate the anti-allergic effect of baicalin on allergic response in ovalbumin (OVA)-induced allergic rhinitis guinea pigs and lipopolysaccharide (LPS)-stimulated human mast cells.. Using in vivo models, we evaluated the effect of baicalin on allergic rhinitis symptoms via recording the number of nasal rubs and sneezes. The levels of histamine, OVA-specific immunoglobulin E(IgE), eosinophil cationic protein (ECP) and inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The histological changes of nasal mucosa were observed by light microscope after HE staining. In vitro, the release of histamine and β-hexosaminidase of compound 48/80-induced human mast cells were measured by ELISA and PNP-NAG colorimetry, respectively. The productions of inflammatory cytokines of LPS-stimulated human mast cells were determined using ELISA. Western blot was used to test the protein expression of JAK2, p-JAK2, STAT5, p-STAT5, IKKβ, p-IKKβ, IκBα, p-IκBα and NF-κB (p65) of LPS-stimulated human mast cells.. The oral administration of baicalin at doses of 50 and 200 mg/kg improved allergic rhinitis symptoms and the histological changes of nasal mucosa and decreased the serum levels of histamine, ECP, interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α and OVA-specific IgE in OVA-induced allergic rhinitis guinea pigs. In vitro, baicalin suppressed the release of histamine and β-hexosaminidase in compound 48/80-induced human mast cells. In addition, baicalin also inhibited the productions of inflammatory cytokines such as IL-1β, IL-6, IL-8 and TNF-α and suppressed the phosphorylation of JAK2, STAT5, IKKβ, IκBα and the nuclear translocation of NF-κB (p65) subunit in LPS-stimulated human mast cells.. These results suggest that baicalin can effectively prevent allergic response in OVA-induced allergic rhinitis guinea pigs and inhibit inflammatory response via blocking JAK2-STAT5 and NF-κB signaling pathways in LPS-stimulated human mast cells. Considered together,the results show that baicalin may be a useful drug in the treatment of allergic rhinitis.

Topics: Animals; Anti-Allergic Agents; Cell Line; Cell Survival; Cytokines; Flavonoids; Guinea Pigs; Humans; Immunoglobulin E; Janus Kinase 2; Lipopolysaccharides; Male; Mast Cells; Nasal Mucosa; NF-kappa B; Ovalbumin; Rhinitis, Allergic; STAT5 Transcription Factor

Nuclear antigens are known to trigger off innate and adaptive immune responses. Recent studies have found that the complex of nucleic acids and core histones that are derived from damaged cells may regulate allergic responses. However, no fundamental study has been performed concerning the role of linker histone H1 in mast cell-mediated type I hyperreactivity. In this study, we explored the impact of histone H1 on mast cell-mediated allergic responses both in vitro and in vivo. In the course of a bona-fide experimental allergen sensitization model upon co-injection with alum adjuvant, ovalbumin (OVA), but not PBS, induced elevated levels of circulating histone H1. Intranasal challenge with histone H1 to OVA/alum- (but not PBS/alum)-sensitized mice induced significantly severer symptoms of allergic rhinitis than those in mice sensitized and challenged with OVA. A monoclonal antibody against histone H1 not only suppressed mast cell degranulation, but also ameliorated OVA-induced nasal hyperreactivity and IgE-mediated passive cutaneous anaphylaxis. Our present data suggest that nuclear histone H1 represents an alarmin-like endogenous mediator acting on mast cells, and that its blockage has a therapeutic potential for mast cell-mediated type I hyperreactivity.

Topics: Allergens; Animals; Antibodies, Neutralizing; Blotting, Western; Disease Models, Animal; Disease Progression; Female; Histones; Immunoenzyme Techniques; Immunoglobulin E; Male; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Passive Cutaneous Anaphylaxis; Peptide Fragments; Rats; Rats, Inbred Lew; Rhinitis, Allergic

To explore the expression and significance of vasoactive intestinal peptide and Pituitary adenylate cyclase activiting polypeptide (VIP/PACAP) of nasal mucosa in rats with allergic rhinitis (AR), and the function of botulinum toxin-A(BTX-A) to inhibit the expression of VIP/PACAP in AR.. Thirty Sprague-Dawley rats were randomly divided into 3 groups, which were the AR group, the intervention group, and the control group. In the AR group, ovalbumin was used to sensitize healthy rats. In the intervention group, BTX-A was dripped into the nasal cavity of AR rats 7 times. In the control group, only physiological saline was used to drip into the nasal cavity of AR rats. Changes of the rats' behavior were observed. ELISA were used to detected the concentration variation of serum IFN-γ and IL-4. Histopathology and immunohistochemistry were employed to observe morphology in the rats' nasal mucosal and the expression of VIP/PACAP. Statistical analysis was also made.. (1)The typical symptoms marks of nasal scratching, sneezing, nasal blockage and rhinorrhea of AR group (7.5 ± 0.50) were higher than intervention group (1 ± 0.27) and control group (0.8 ± 0.31). (2) Comparing to intervention group and control group, the serm IFN-γ of the AR group obvious reduced (P < 0.05), the serm IL-4 of the AR group obvious rose (P < 0.01), and the serm Th1/Th2 (IFN-γ/IL-4) of the AR group obvious reduced (P < 0.01). (3) Comparing to intervention group and control group, the cilium loss, inflammatory cells infiltration, and inflammatory cells exudation of nasal mucosa in AR group were more obviously (P < 0.01), and the intervention group of the 3 indexes was obviously than control group. (4) The expression of VIP in the rats' nasal mucosa of the AR group (13.27 ± 2.74) were more intense than intervention group (5.21 ± 2.18) and control group (3.56 ± 5.30) (P < 0.01), and the expression of PACAP in the rats' nasal mucosa of the AR group (20.97 ± 2.14) were more intense than intervention group (6.33 ± 3.04) and control group (4.63 ± 1.25) (P < 0.01). (5) In all the 3 groups, there was positive correlation between expression of negative in VIP/PACAP and Thl/Th2 cell infiltration(r were respectively -0.340 and -0.223, P < 0.05).. The VIP/PACAP in the rats' nasal mucosa may play an important role in pathogenesis of AR, and BTX-A could improve the symptoms of AR through inhibition of the expression of VIP/ PACAP.

Topics: Animals; Botulinum Toxins, Type A; Disease Models, Animal; Interferon-gamma; Interleukin-4; Nasal Mucosa; Ovalbumin; Paranasal Sinuses; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Vasoactive Intestinal Peptide

We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during induction of asthma/rhinitis. Group D showed significantly decreased eosinophils, neutrophils, and lymphocytes in their BAL fluid compared with groups B and C (p < 0.05). In real-time polymerase chain reaction using lung homogenate, the expression of IL-1β was significantly upregulated (p < 0.001) and IL-4 and IL-10 significantly downregulated (p < 0.05) in group D. Infiltration of inflammatory cells into lung parenchyma and turbinate, and the thickness of respiratory epithelium was significantly reduced in group D (p < 0.05). The expression of Bcl-2 and heme oxygenase-1 were significantly downregulated, Bax and extracellular dismutase significantly upregulated in Group D. Therefore, chronic hypergravity could have a hormetic effect for allergic asthma and rhinitis via regulation of genes involved in antioxidative and proapoptotic pathways. It is possible that we could use hypergravity machinery for treating allergic respiratory disorders.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Gene Expression Regulation; Heme Oxygenase-1; Hormesis; Hypergravity; Immunoglobulin E; Interleukin-10; Interleukin-1beta; Interleukin-4; Membrane Proteins; Mice; Mice, Inbred BALB C; Ovalbumin; Proto-Oncogene Proteins c-bcl-2; Rhinitis, Allergic

Allergic rhinitis (AR) has been a significant healthcare burden on individuals and society. However, the detailed effect of different patterns of allergen exposure on the development of AR remains controversial. A mouse model of AR was established to address the complex relationships between allergen exposure and the development of AR. Allergic symptom, OVA-specific IgE in serum and nasal lavage fluid, allergic inflammation in nasal tissues were evaluated after intranasal sensitization and challenge of ovalbumin (OVA) in mice treated with two different doses of allergen for different sensitized durations. Exposure to different doses and sensitized durations of OVA were capable of inducing allergic nasal response. Repetitive OVA exposure in the sensitization phase induced the recruitment of eosinophils and goblet cell hyperplasia. The level of OVA-specific IgE in serum depended on OVA exposure and was mediated in a duration-related manner. In addition, mice treated with low-dose OVA for prolonged duration manifested the major features of human local allergic rhinitis. There were dose- and duration-related effects of allergen exposure on the development of AR. LAR was associated with repetitive exposure to low-dose allergen. Thus, allergen avoidance should be an important aim of AR management.

Topics: Administration, Intranasal; Allergens; Animals; Biomarkers; Environmental Exposure; Female; Immunoglobulin E; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Random Allocation; Rhinitis, Allergic

The posterior nasal nerve is the dominant source of the parasympathetic, sympathetic, and sensory fibers that innervate the nasal respiratory mucosa. Therefore, a posterior nasal neurectomy (PNN) is thought to induce denervation of the nasal mucosa and relieve the nasal symptoms of allergic rhinitis. However, the underlying mechanisms and therapeutic action of PNN remain unknown. To investigate the impact of PNN-induced denervation of the nasal mucosa on allergic rhinitis, we developed a rat model of PNN and examined the effects of PNN on allergic rhinitis in ovalbumin-sensitized rats. This rat model of PNN was characterized by the depletion of nerve fibers, choline acetyltransferase, and neuropeptides (eg, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and neuropeptide Y) in the nasal respiratory mucosa. These animals exhibited nasal gland and goblet cell hypertrophy in the septal mucosa and atrophy of the submucosal gland in the lateral nasal wall, as well as reduced nasal secretion due to deficient acetylcholine synthesis. In an ovalbumin-sensitized model of allergic rhinitis, PNN also induced the depletion of nerve fibers, choline acetyltransferase, and neuropeptides in the nasal mucosa and suppressed nasal secretion. However, PNN did not affect mucosal thickening, eosinophil and mast cell infiltration, interleukin-4 and interferon-γ mRNA expression, and allergic symptoms (ie, sneezing and nasal scratching). These results suggest that the peripheral nerves and corresponding neuropeptides regulate nasal secretion, but not hypersensitivity, in allergic rhinitis, and that allergic rhinitis-related mucosal reactions occur in a highly denervated mucosa after PNN. Posterior nasal neurectomy may be a therapeutic option for the treatment of hyperrhinorrhea, but not allergic rhinitis hypersensitivity.

Topics: Animals; Choline O-Acetyltransferase; Cytokines; Denervation; Disease Models, Animal; Fluorescent Antibody Technique; Gene Expression; Humans; Male; Nasal Mucosa; Nasal Surgical Procedures; Neuropeptides; Neurosurgical Procedures; Ovalbumin; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis, Allergic

Patients with chronic rhinosinusitis (CRS) commonly experience aggravation of their symptoms after viral upper respiratory infection (URI). Rhinovirus (RV) is the most common URI-causing virus. However, there is a lack of a mouse model of RV infection and in vivo studies investigating the effect of RV infection on CRS.. A mouse model of chronic allergic rhinosinusitis (CARS) was established by sensitizing to ovalbumin (OVA) through intraperitoneal injection followed by nasal challenges with OVA for 5 weeks. Both control and CARS mice were euthanized at 48 hours after infection with minor group RV serotype 1B (RV1B). Sinonasal complex samples were evaluated histologically; and interleukin (IL)-6, macrophage inflammatory protein (MIP)-2, IL-13, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured in the nasal lavage fluid. The RV1B-infected areas in control and CARS mice were identified using immunofluorescence.. In the infected control mice group, RV1B increased secretory hyperplasia in the sinonasal mucosa and the production of proinflammatory cytokines including INF-γ, MIP-2, and IL-13. Immunohistochemical analysis of nasal mucosa from RV1B-infected mice presented abundant RV1B staining, which was distributed between the epithelium and the lamina propria. In the CARS group, the RV1B-infected area per unit was significantly higher than that in control mice. However, RV1B infection neither increased the proinflammatory cytokine secretion nor worsened the histology significantly.. We successfully established a mouse model of upper airway RV infection by nasal inoculation with RV1B. Although there was histologically-proven increased RV infection in the CARS model, the infection did not intensify sinonasal inflammation.

Topics: Allergens; Animals; Chronic Disease; Cytokines; Disease Models, Animal; Female; HeLa Cells; Humans; Mice, Inbred BALB C; Nasal Lavage Fluid; Nasal Mucosa; Ovalbumin; Picornaviridae Infections; Rhinitis, Allergic; Rhinovirus; Sinusitis

To study the role of JNK (c-Jun N-terminal kinase) signal transduction pathway on the nasal mucosa remodeling in allergic rhinitis rats, to explore whether IL-1β participates the nasal mucosa remodeling in allergic rhinitis by JNK signal transduction pathway.. Totally 60 male Wistar rats (weighing about 200-250 g)were randomly divided into A (AR group) and B group (control group). The rats in A group were sensitized for inducing AR by intraperitoneal injection ovalbumin and Al(OH)₃. Ovalbumin was respectively dropped in each nasal cavity of every rat for 4,8,12 weeks(A4,A8,or A12 group) each had 10 rats. The rats in B group were sensitized by intraperitoneal injection saline. Saline was respectively dropped in each nasal cavity of every rat for 4,8, 12 weeks(B4, B8, or B12 group), and each had 10 rats. The concentration of IL-1β in serum and nasal lavage fluid were tested by ELASA. The protein expressions of P-JNK and P-c-Jun were detected by immunohistochemical technique. Linear correlation analysis showed the correlation between levels of IL-1β in serum and P-JNK protein, levels of IL-1β in nasal lavage fluid and P-JNK protein.. The concentrations of IL-1β in serum and nasal lavage fluid of A group were all significantly higher than those of the corresponding B group (all P < 0.01). Compared with A4 group and A8 group, concentrations of IL-1β in nasal lavage fluid of A12 group were significantly increased (all P < 0.01). However the levels of IL-1β in serum were not significantly different among them (all P > 0.05). Mean absorbance values of P-JNK and P-c-Jun in A group were significantly higher than those in corresponding B group (all P < 0.01) and compared with A4 group and A8 group, those of A12 group were significantly increased (all P < 0.01). Strong positive correlation were found between P-JNK and concentration of IL-1β in serum or nasal lavage fluid (r = 0.835 and r = 0.902, all P < 0.01).. JNK signal transduction pathway plays important role in the nasal mucosa remodeling in allergic rhinitis rats. IL-1β participates in AR nasal mucosa remodeling possibly partly through activating JNK signal transduction pathway.

Topics: Animals; Disease Models, Animal; Interleukin-1beta; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Signaling System; Nasal Mucosa; Ovalbumin; Paranasal Sinuses; Rats; Rats, Wistar; Rhinitis, Allergic; Signal Transduction

Defective innate immune functions can contribute to chronic rhinosinusitis (RS). Recently, it has been reported that chronic RS patients show impaired function of natural killer (NK) cells. We investigated the role of NK cells in eosinophilic inflammation in an allergic RS mouse model.. Mice sensitized to ovalbumin (OVA) by intraperitoneal injection received nasal challenges with OVA for 5 weeks. NK cell depletion was achieved by intraperitoneal injections of anti-asialo ganglio-N-tetraosylceramide (ASGM1) antibodies 10 days before OVA sensitization and every 5 days thereafter until sacrifice. Sinonasal complex samples were evaluated histologically, and IL-4, IL-5, IL-13, IFN-γ, MIP-2, and eotaxin levels were measured in the nasal lavage fluid. Differential white blood cell counts were also obtained.. Allergic RS mice showed significantly more eosinophilic inflammation in the sinonasal mucosa, elevated levels of IL-4, IL-5, IL-13, and eotaxin in the nasal lavage fluid, and peripheral blood eosinophilia compared to control mice. The depletion of NK cells by anti-ASGM1 treatment induced more prominent eosinophilic inflammation and increased secretion of IL-5 and peripheral blood eosinophilia in allergic RS mice.. The depletion of NK cells aggravates allergen-induced sinonasal eosinophilic inflammation, suggesting that impaired NK cell activity may be an exacerbating factor in eosinophilic chronic RS.

Topics: Allergens; Animals; Biopsy, Needle; Cytokines; Disease Models, Animal; Female; Immunity, Innate; Immunohistochemistry; Killer Cells, Natural; Lymphocyte Count; Mice; Mice, Inbred BALB C; Nasal Lavage Fluid; Nasal Mucosa; Ovalbumin; Random Allocation; Reference Values; Rhinitis, Allergic; Sensitivity and Specificity; Sinusitis

To establish the murine models of local allergic rhinitis (LAR) and allergic rhinitis (AR) by using ovalbumin (OVA), and to investigate the relationship between them.. Thirty BALB/c mice were divided into 5 groups, (1) the nasally sensitized group (group A1) that was challenged with OVA by a 10 d procedure, (2) the control group of A1 that was challenged with phosphate-buffered saline (PBS), (3) the nasally sensitized group (group A2) that was challenged with OVA by a 25 d procedure, (4)the control group of A2 that was challenged with PBS, (5) the intraperitoneally sensitized group (group B) .The numbers of sneezing after final challenge were counted, and the serum OVA-specific immunoglobulin E (OVA-sIgE), interleukin (IL) -4, IL-13, IL-5 levels in nasal lavage fluid were measured by ELISA. Hematoxylin-eosin staining was performed to evaluate the histological change of nose and lung tissues. Graph Pad Prism 6 software was used to analyze the data.. Nasally sensitized group A1 displayed LAR symptoms of sneezing and eosinophilic infiltrating, but without increased OVA-sIgE in serum on day 10 compared with the control group of A1(t=0.697, P>0.05), OVA-sIgE in serum of group A2(2.710±1.406)ng/ml reached to statistical significance and with airway remodeling on day 25 compared with the control group of A2((0.221±0.080)ng/ml, t=4.329, P<0.05). IL-5 and IL-13 in nasal fluid showed a significant increase in the nasally sensitized group A1, compared with the group A2(t values were 2.442, 2.804, P values were less then 0.05).. A short time intranasal instillation with OVA could establish LAR murine model, continuing OVA challenge could increase serum sIgE level and with airway remodeling. LAR mice show a unique characteristic by expressing higher IL-5 and IL-13 in nose than AR mice, but sIgE in serum remains at a normal level.

Topics: Administration, Intranasal; Animals; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Eosinophils; Immunoglobulin E; Interleukin-13; Interleukin-4; Interleukin-5; Lung; Mice; Mice, Inbred BALB C; Nose; Ovalbumin; Rhinitis, Allergic; Sneezing; Sodium Chloride

Recent studies have implicated that Hypoxia-inducible factor 1α (HIF-1α) plays an integral role in the pathogenesis of allergic rhinitis and asthma. In the present study, we showed that HIF-1α antagonist YC-1, 3-(5-hydroxymethyl-2-furyl)-1-benzylindazole, elicited a potent allergy-ameliorating effect in a rat model of ovalbumin (OVA)-sensitized combined allergic rhinitis and asthma syndrome (CARAS). We revealed that YC-1 administration markedly impaired the total number and percentage of eosinophil in bronchoalveolar lavage fluid (BAL Fluid) of the rats, suggesting that YC-1 might attenuate lung and nasal mucosal inflammation in OVA-sensitized rats. Moreover, histological examination found that OVA-induced pathological alterations were evidently attenuated following YC-1 administration. In addition, immunohistochemistrial analysis indicated that YC-1 treatment decreased the expression of HIF-1α in rat lungs and nasal mucosa. Notably, Nuclear factor kappa B (NF-κB) p65 and Peroxisome proliferator-activated receptor α (PPARα), two important regulators of inflammatory responses, were also significantly down-regulated following YC-1 administration. Real-time PCR analysis confirmed that YC-1 impaired the expression of HIF-1α, NF-κB and PPARα in CARAS model. These findings together indicated that YC-1 exerted remarkable anti-allergic effects through the modulation of inflammatory pathways, implying that YC-1 may potentially serve as a novel anti-CARAS medicine in clinical patients.

Topics: Animals; Anti-Allergic Agents; Asthma; Gene Expression Regulation; Hypoxia-Inducible Factor 1, alpha Subunit; Indazoles; Lung; Male; Nasal Mucosa; Ovalbumin; PPAR alpha; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; RNA, Messenger; Transcription Factor RelA

We selected a hit compound, 2-(4-{2-[(phenylthio)acetyl]-carbonohydrazonoyl}-phenoxy)acetamide (PA), by a molecular docking simulation between 636,565 compounds and caspase-1 protein. We examined the effect of PA on allergic rhinitis (AR) animal model.. We assessed the therapeutic effects and the regulatory mechanisms of ovalbumin (OVA)-sensitized mouse model of AR.. A molecular docking simulation and a kinetic assay indicated that PA regulates the caspase-1 activation through the interaction with the caspase-1 active site. In the AR animal model, PA significantly reduced the rub scoring increased by OVA. The up-regulated IgE, histamine, interleukin (IL)-1β, and thymic stromal lymphopoietin (TSLP) levels in the serum of OVA-sensitized mice were significantly decreased by the treatment with PA. Protein levels of IL-1β, IL-5, IL-6, IL-13, tumor necrosis factor-α, TSLP, cyclooxygenase-2, macrophage inflammatory protein-2, and intercellular adhesion molecule-1 were also significantly inhibited by the treatment with PA in the nasal mucosa tissues of the OVA-sensitized mice. In the PA-treated mice, the number of eosinophils and mast cells infiltrated by OVA-sensitization were also reduced. In addition, PA reduced the mast cell-derived caspase-1 activity and expression in the nasal mucosa tissues of the OVA-sensitized mice.. PA showed the possibility to regulate AR in OVA-induced AR models, suggesting that it has therapeutic potential for the management of AR as a lead compound.

Topics: Acetamides; Allergens; Animals; Anti-Allergic Agents; Caspase 1; Cell Line; Cell Survival; Cyclooxygenase 2; Cytokines; Female; Histamine; Humans; Hydrazones; Immunoglobulin E; Mice, Inbred BALB C; Molecular Docking Simulation; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Spleen

This study aimed to explore the effects of curcumin on experimental allergic rhinitis in rats.. Twenty-eight male Wistar albino rats were randomly divided into four groups: a control group; a group in which allergic rhinitis was induced and no treatment given; a group in which allergic rhinitis was induced followed by treatment with azelastine hydrochloride on days 21-28; and a group in which allergic rhinitis was induced followed by treatment with curcumin on days 21-28. Allergy symptoms and histopathological features of the nasal mucosa were examined.. The sneezing and nasal congestion scores were higher in the azelastine and curcumin treatment groups than in the control group. Histopathological examination showed focal goblet cell metaplasia on the epithelial surface in the azelastine group. In the curcumin group, there was a decrease in goblet cell metaplasia in the epithelium, decreased inflammatory cell infiltration and vascular proliferation in the lamina propria.. Curcumin is an effective treatment for experimentally induced allergic rhinitis in rats.

Topics: Administration, Intranasal; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Chondrocytes; Cilia; Curcumin; Eosinophils; Goblet Cells; Hyperemia; Hypertrophy; Male; Mast Cells; Metaplasia; Nasal Mucosa; Ovalbumin; Phthalazines; Random Allocation; Rats; Rats, Wistar; Rhinitis, Allergic; Sneezing

Sublingual immunotherapy (SLIT) is a safe and effective treatment for allergic rhinitis (AR). However, many issues regarding SLIT remain to be resolved, including the optimal timing of administration. This study investigated the effect of time of day on SLIT efficacy with the goal of optimizing the therapeutic outcome.. We performed prophylactic SLIT at different times of day (10 a.m. or 10 p.m.) in 2 mouse models of AR: an ovalbumin (OVA)-induced AR model and Cry j 1-induced AR model, and compared the effects.. In the OVA-induced AR model, mice sublingually receiving OVA at 10 a.m. exhibited a greater decrease in total and OVA-specific IgE levels than mice treated at 10 p.m. In addition, mice treated at 10 a.m. exhibited reductions in OVA-specific IL-4, IL-10, and IL-13 production by splenocytes relative to mice treated at 10 p.m. Furthermore, we observed a more efficient capture of sublingually administered OVA in submandibular lymph nodes at 10 a.m. than at 10 p.m. in mice. Similar results were observed in the Cry j 1-induced AR model using Japanese cedar pollen extract for SLIT.. Given the allergen-specific antibody and T cell responses, we suggest that SLIT may be more effective in the resting phase than in the active phase (note that mice are nocturnal animals). Thus, we propose that a chronotherapeutic approach should be considered for SLIT to maximize its effectiveness.

Topics: Allergens; Animals; Biomarkers; Disease Models, Animal; Female; Immunoglobulin E; Immunoglobulin G; Mice; Ovalbumin; Phenotype; Rhinitis, Allergic; Sublingual Immunotherapy; Treatment Outcome

Allergic rhinitis (AR) is a common worldwide disease. Animal studies on AR were adopted in various investigations. However, animal studies simply aimed at establishing an animal model for AR have been seldom seen. The purpose of this study was to introduce an easy-to-establish experimental mouse model of AR. To develop a mouse model of AR, 38 Balb/c mice were randomly assigned to two groups. Mice in the study group were sensitized by intraperitoneal (IP) injection of ovalbumin (OVA) on day 1 and 6, followed by continuous inhalation (IH) of OVA solution for 1 week (day 8-14) using a newly designed inhalation box. The control group mice received sensitization of IP normal saline and IH sterilized distilled water instead of OVA. Before and after sensitization, the frequencies of nasal symptoms (sneezing, nasal rubbing) were recorded and the serum levels of total immunoglobulin E (IgE) were evaluated using ELISA. Finally, the murine nasal mucosal tissues were stained by Giemsa solution to estimate the degree of mast cell infiltration. After sensitization by IP and IH OVA, the study group showed significant phenotypic changes including increased sneezing and rubbing. Pathological and cytological findings also confirmed significant elevated serum total IgE titer and local mast cell infiltration in the study group statistically. We successfully developed a workable experimental animal model for AR that was more easily sensitized using our new-designed inhalation box, with less stress and more precisely to be observed.

Topics: Allergens; Animals; Disease Models, Animal; Drug Administration Routes; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sneezing

T helper type 2 (Th2) cells, which produce interleukin-4 (IL-4), IL-5 and IL-13, control immunity to all forms of allergic inflammatory responses. Interleukin-21 (IL-21) reduces allergic symptoms in murine models and inhibits IL-4-induced IgE secretion by B cells. However, whether or not IL-21 directly affects Th2 cells, which leads to reduced allergic symptoms, is unclear. In this study, we investigated the effects of IL-21 on the differentiation and effector functions of Th2 cells. We found that IL-21 reduced the number of differentiated Th2 cells and these Th2 cells showed a diminished Th2 cytokine production. Interleukin-21 suppressed Th2 cytokine production of already polarized Th2 cells by down-regulation of transcription factor GATA-3. It also induced apoptosis of Th2 cells with decreased anti-apoptotic factor Bcl-2. Intranasal administration of IL-21 at the beginning of ovalbumin (OVA) sensitization or before OVA challenge decreased Th2 cytokines in the bronchoalveolar lavage fluid of OVA/alum-immunized allergic mice. In addition, the inhibitory effects of IL-21 on Th2 effector functions can also be found in allergic patients. Our results demonstrate that IL-21 suppresses the development of Th2 cells and functions of polarized Th2 cells. Hence, the administration of IL-21 may be considered for use as a preventive and therapeutic approach when dealing with Th2-mediated allergic diseases.

Topics: Animals; Anti-Allergic Agents; Apoptosis; Case-Control Studies; Cell Differentiation; Cells, Cultured; Disease Models, Animal; Female; GATA3 Transcription Factor; Genes, T-Cell Receptor; Humans; Interleukins; Mice, Inbred BALB C; Mice, Transgenic; Ovalbumin; Phenotype; Proto-Oncogene Proteins c-bcl-2; Recombinant Proteins; Respiratory Hypersensitivity; Rhinitis, Allergic; Th2 Cells

We have previously demonstrated that anti-IL-1β immunoglobulin yolk(IgY) inhibits pathological responses in allergic asthma guinea pigs induced by ovalbumin(OVA). This study aims to determine whether the combined blockade of IL-1β and TNF-α can more effectively inhibit allergic inflammation in allergic rhinitis(AR) guinea pigs induced by OVA. Healthy guinea pigs treated with saline were used as the healthy control. The AR guinea pigs induced by OVA were randomly divided into (1) the AR model group containing negative control animals treated with intranasal saline; (2) the 0.1% non-specific IgY treatment group treated with non-specific IgY; (3) the 0.1% anti-TNF-α IgY treatment group treated with 0.1% anti-TNF-α IgY; (4) the 0.1% anti-IL-1β IgY treatment group treated with 0.1% anti-IL-1β IgY; (5) the 0.1% combined anti-IL-1β IgY and anti-TNF-α IgY treatment group treated with 0.1% combined anti-IL-1β IgY and anti-TNF-α IgY; and (6) the fluticasone propionate treatment group treated with fluticasone propionate. Cytokines were measured using an enzyme-linked immunosorbent assay. The results showed that IL-1β, IL-5, IL-9, IL-13, IL-18, IL-22, IL-33, TNF-α, TGF-β1 and OVA-specific IgE levels in the peripheral blood (PB) and nasal lavage fluid (NLF) significantly decreased at 2h, 4h or 8h in the 0.1% combined anti-IL-1β IgY and anti-TNF-α IgY treatment group compared to the AR model group and the 0.1% non-specific IgY treatment group (P<0.05). The data suggest that blockade of IL-1β and TNF-α by intranasal instillation of combined anti-IL-1β IgY and anti-TNF-α IgY could be a potential alternative strategy for preventing and treating allergic rhinitis.

Topics: Allergens; Animals; Anti-Inflammatory Agents; Antibodies, Blocking; Disease Models, Animal; Drug Therapy, Combination; Guinea Pigs; Humans; Immunoglobulin E; Immunotherapy; Interleukin-1beta; Male; Ovalbumin; Rhinitis, Allergic; Tumor Necrosis Factor-alpha

The objective of the present work was to evaluate anti-allergic effects of intranasal administration of type-A procynidines polyphenols (TAPP) based standardized hydroalcoholic extract of Cinnamomum zeylanicum bark (TAPP-CZ) in ovalbumin (OVA)-induced experimental allergic rhinitis (AR) in BALB/c mice. Sixty male BALB/c mice were divided into six groups of ten each (G1-G6). The mice from G1 were nonsensitized and maintained as normal group. Remaining mice (G2-G6) were sensitized with OVA (500 μL solution, intraperitoneal) on alternate days for 13 days and had twice daily intranasal treatment from day 14-21 as follows: G2 (AR control) received saline, G3 (positive control, XLY) received xylometazoline (0.5 mg/mL, 20 μL/nostril) and G4-G6 received TAPP-CZ (3, 10 and 30 µg/kg in nostril), respectively. On day 21, mice were challenged with OVA (5 μL/nostril, 5% solution) and assessments (nasal signs, biochemical and histopathological) were performed. Treatment with TAPP-CZ (10 and 30 µg/kg in nostril) showed significant attenuation in OVA-induced alterations of the nasal (number of nasal rubbing and sneezing), biochemical markers (serum IgE and histamine), haematological, morphological (relative organ weight of spleen and lung) and histopathological (nasal mucosa and spleen) parameters. In conclusion, TAPP-CZ showed anti-allergic efficacy in animal model of AR.

Topics: Administration, Intranasal; Animals; Anti-Allergic Agents; Biflavonoids; Catechin; Cinnamomum zeylanicum; Disease Models, Animal; Histamine; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Bark; Plant Extracts; Polyphenols; Proanthocyanidins; Rhinitis, Allergic; Sneezing

High-mobility group box 1 (HMGB1) protein, a pro-inflammatory DNA-binding protein, meditates inflammatory responses through Toll-like receptor-4 signals and amplifies allergic inflammation by interacting with the receptor for advanced glycation end products. Previous studies have shown that HMGB1 is elevated in the nasal lavage fluids (NLF) of children suffering from allergic rhinitis (AR) and is associated with the severity of this disease. Furthermore, HMGB1 has been implicated in the pathogenesis of lower airway allergic diseases, such as asthma. Ethyl pyruvate (EP) has proven to be an effective anti-inflammatory agent for numerous airway diseases. Moreover, EP can inhibit the secretion of HMGB1. However, few studies have examined the effect of EP on AR. We hypothesized that HMGB1 plays an important role in the pathogenesis of AR and studied it using an AR mouse model. Forty BALB/c mice were divided into four groups: the control group, AR group, 50 mg/kg EP group, and 100 mg/kg EP group. The mice in the AR and EP administration groups received ovalbumin (OVA) sensitization and challenge, whereas those in the control group were given sterile saline instead of OVA. The mice in the EP administration group were given an intraperitoneal injection of EP 30 min before each OVA treatment. The number of nasal rubbings and sneezes of each mouse was counted after final treatment. Hematoxylin-eosin staining, AB-PAS staining, interleukin-4 and 13 in NLF, IgE, and the protein expression of HMGB1 were measured. Various features of the allergic inflammation after OVA exposure, including airway eosinophilia, Th-2 cytokine production, total IgE, and goblet cell hyperplasia were significantly inhibited by treatment with EP and the expression and release of HMGB1 were reduced after EP administration in a dose-dependent manner. These results indicate that HMGB1 is a potential therapeutic target of AR and that EP attenuates AR by decreasing HMGB1 expression.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; HMGB1 Protein; Immunoglobulin E; Immunohistochemistry; Inflammation; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Pyruvates; Rhinitis, Allergic; Toll-Like Receptor 4; Up-Regulation

This study is aimed at exploring the effect of Bencycloquidium bromide (BCQB), a novel M1/M3 receptor antagonist, on mucus secretion in a murine model of allergic rhinitis (AR).. Sprague-Dawley rats were sensitized with ovalbumin to induce AR. After BCQB treatment, nasal symptoms were evaluated. Nasal lavage fluid was used to detect the protein level of cytokines and histamine by the method of enzyme-linked immunosorbent assay. The nasal mucosa of all animals was prepared for western blot, quantitative real-time polymerase chain reaction and histochemical analysis.. BCQB could not only alleviate typical AR symptoms including rhinorrhea, nasal itching and sneezing, but also inhibit the overexpression of mucin 5AC at the level of protein and mRNA. The release of histamine, the mRNA and protein level of IL-6, IL-13 and TNF-α, and the nuclear translocation of NF-κB (p65 and p50) were inhibited by BCQB. In addition, histological studies showed BCQB dramatically inhibited ovalbumin-induced nasal lesions, eosinophil infiltration, aggregation of mast cells, globlet cell hyperplasia and metaplasia.. BCQB attenuates mucus hypersecretion in AR, possibly involving in the NF-κB signaling pathway.

Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Cytokines; Disease Models, Animal; Histamine; Male; Nasal Lavage Fluid; Nasal Mucosa; NF-kappa B; Ovalbumin; Rats; Rats, Sprague-Dawley; Receptor, Muscarinic M1; Receptor, Muscarinic M3; Rhinitis, Allergic; Signal Transduction

The aim of this study was to determine whether allergic rhinitis can induce structural changes in the synapse formation in the hippocampus of BALB/c mice immunocytochemically.. Allergic rhinitis was induced in mice by two intra-peritoneal injections of ovalbumin administered with a one-week interval. After two weeks, the sensitised mice were challenged with an intra-nasal injection of ovalbumin for two weeks. To analyse the hippocampal synaptic structures, sections were immunostained with antibodies against glutamic acid decarboxylase 65 and glutamic acid decarboxylase 67 (for γ-aminobutyric acid-ergic terminals), synaptophysin (for glutamatergic and γ-aminobutyric acid-ergic terminals) and spinophilin (for dendritic spines). The number of nasal rubbing movements was significantly greater in the allergic rhinitis mice than in the control mice. However, the expression patterns of the four above-mentioned synaptic markers in the hippocampus showed no detectable difference between the allergic rhinitis and control mice.. These data indicate that the synaptic structure in the hippocampus might remain unaltered in allergic rhinitis patients.

Topics: Administration, Intranasal; Allergens; Animals; Dendritic Spines; Disease Models, Animal; gamma-Aminobutyric Acid; Glutamate Decarboxylase; Hippocampus; Mice; Mice, Inbred BALB C; Microfilament Proteins; Nerve Tissue Proteins; Ovalbumin; Rhinitis, Allergic; Synapses; Synaptophysin

Allergic rhinitis (AR) is a global health problem that affects a large number of population. Piperine (PIP) has been reported to exhibit anti-inflammatory, anti-histaminic, and immunomodulatory activities; however, its antiallergic profile has not been studied.. The objective of the study was to investigate the antiallergic potential of PIP in ova-albumin (OVA)-induced AR, mast cell degranulation (MSD), and OVA-induced paw edema.. Mice were sensitized with OVA alternately on 1, 3, 5, 7, 9, 11, and 13th day. They were treated with either vehicle, PIP (10, 20, and 40 mg/kg, p.o.), or montelukast (10 mg/kg, p.o.) from the 14th to 20th day. On the 21st day, intranasal (OVA: 5% µl) challenge was done. Animals were evaluated for physiological parameters, biochemical parameters, spleen weight, expression of interleukins (IL-6 and IL-1β), and immunoglobin-E (IgE). Histopathology of nasal mucosa, lungs, and spleen was carried out. MSD and paw edema studies were made to understand the mechanism of action.. PIP (10, 20, and 40 mg/kg, p.o.) showed a significant dose-dependent protection with respect to nasal rubbing, redness of nose, and sneezing (p < 0.001) following nasal challenge. PIP dose dependently reduced histamine, NO concentration (p < 0.001), as well as reduced expression of IL-6, IL-1β, and IgE (p < 0.001) as compared with the control group. Histopathology showed inhibition of infiltration of eosinophils and hyperplasia. It dose dependently reduced MSD and paw edema (p < 0.001).. PIP acts by mast cell-stabilizing activity, exhibits immunomodulatory and anti-inflammatory activity, thereby providing an effective treatment for AR.

Topics: Acetates; Alkaloids; Animals; Anti-Allergic Agents; Benzodioxoles; Biomarkers; Cell Degranulation; Cyclopropanes; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Eosinophils; Histamine; Immunoglobulin E; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Mast Cells; Nitric Oxide; Ovalbumin; Piperidines; Polyunsaturated Alkamides; Quinolines; Rhinitis, Allergic; Spleen; Sulfides; Time Factors

To detect the expression and explore the role of the innate immune NLRP3 inflammasome and its downstream factors interleukin-1β (IL-1β)/ interleukin-18 (IL-18) in rat model of allergic rhinitis (AR).. Forty Sprague Dawley (SD) rats were randomly divided into control group (A group), AR model group 1 (B group), AR model group 2(C group), AR model group 3 (D group). Every group contained 10 rats. After the rats in the model group were sensitized by ovalbumin (OVA) and alum, B, C and D groups were separately stimulated with 5% OVA for 10 days, 20 days and 30 days (once a day). The control group did not add OVA in the process of sensitization and excitation. All rats were executed after excitation.Eosinophil granulocyte (EOS) infiltration were observed in nasal mucosa by hematoxylin-eosin (HE) staining, the expression of NLRP3 and cysteinyl aspartate-specific protease-1 (Caspase-1) were observed in nasal mucosa by immunohistochemical staining. The concentrations of ovalbumin specific IgE (OVA-sIgE), IL-18 and IL-1β in peripheral blood and the concentrations of IL-18 and IL-1β in nasal fluid were tested by enzyme-linked immunosorbent assay (ELISA). The data were processed by SPSS 17.0 software.. EOS cell counted, the behavioral score and the concentrations of OVA-sIgE in AR model group were obviously higher than those in control group (P < 0.05), and the difference of which had statistical significance between the AR model groups (P < 0.05). The expression of NLRP3 in AR model group (The expression of NLRP3 in group of B, C and D were 48.80 ± 10.75, 71.80 ± 16.98 and 100.32 ± 13.91, respectively) were obviously higher than those in control group (17.47 ± 5.59), the difference of which had statistical significance (F = 78.399, P < 0.05). The expression of Caspase-1 in AR model group (The expression of Caspase-1 in group of B, C and D were 36.33 ± 4.71, 50.87 ± 11.18 and 73.10 ± 14.77, respectively) were obviously higher than those in control group (11.48 ± 2.70), the difference of which had statistical significance (F = 71.727, P < 0.05). The concentrations of IL-1β in AR model group [The concentrations of IL-1β in group of B, C and D were (56.46 ± 10.13), (82.37 ± 11.93), (112.01 ± 22.91) pg/ml, respectively] were obviously higher than those in control group [(38.26 ± 4.66) pg/ml], the difference of which had statistical significance (F = 51.981, P < 0.05). The concentrations of IL-18 in AR model group [The concentrations of IL-18 in group of B, C and D were (177.92 ± 23.63), (194.33 ± 20.78), (234.06 ± 31.70) pg/ml, respectively] were obviously higher than those in control group [(89.71 ± 5.56) pg/ml], the difference of which had statistical significance (F = 73.295, P < 0.05). And the difference of which had statistical significance between the AR model groups (P < 0.05). The expression of NLRP3 was significantly positively correlated with the behavioral score, the concentrations of OVA-sIgE and EOS cell counted in rat model of allergic rhinitis (r value were 0.833,0.873 and 0.868, respectively, all P < 0.01).. NLRP3 inflammasome and its downstream factors IL-1β/IL-18 play a role in the pathogenesis of allergic rhinitis, which may be correlated with the degree of inflammation.

Topics: Animals; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Eosinophils; Inflammasomes; Inflammation; Interleukin-18; Interleukin-1beta; Nasal Mucosa; Ovalbumin; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic

Although there have been many studies revealing the mechanism and establishing the therapeutical method for allergic rhinitis, no suitable animal models for allergic rhinitis, especially for pollen allergy, are currently available. We therefore aimed in this study to develop a murine model producing IgE in response to an inhaled antigen without using any adjuvants. Ovalbumin (OVA)-specific T cell receptor transgenic mice (DO11.10) inhaled an OVA solution for one h, twice a week, for six weeks. The resulting increase of OVA-specific IgE in the serum was observed depending on the times of inhalation. Spleen cells from mice that had inhaled the antigen produced more IL-4 and less IFN-γ than those from the control mice in vitro. These results indicate that inhaled antigen enhanced the Th2-type responses and induced IgE production in a T cell-mediated manner. Our findings would contribute to studies on prevention and treatment of pollen allergy.

Topics: Allergens; Animals; Antigens; Disease Models, Animal; Humans; Immunoglobulin E; Interferon-gamma; Interleukin-4; Male; Mice; Mice, Transgenic; Ovalbumin; Receptors, Antigen, T-Cell; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Th2 Cells

To examine AMCase mRNA expression levels in nasal mucosa of allergic rhinitis SD rats.. Thirty SD rats were chosen and randomly divided into the experimental group and the control group. 20 in experimental group and 10 in the control group. AR model rats were established through repeated intraperitoneal shot of ovalbumin (OVA) for 2 weeks and consequently confirmed by local challenge with OVA for 1 week. The control group was treated by the same method with Physiological saline water instead of OVA. After the last excitation allergic rhinitis was diagnosed according to the accumulation score about nasal symptom. The septal mucosa of all rats were used to diagnose pathologically by HE dyeing. AMCase mRNA in nasal mucosa, obtained from the bilateral nasal mucosa in two groups, were used to do reverse transcriptive polymerase chain reaction. Real-time polymerase chain reaction was used to examine AMCase mRNA expression levels.. (1) The results showed definitely that there were positive expression of AMCase mRNA in normal nasal mucosa. This expression increase significantly during nasal allergy (P < 0.05). (2) The increased expression of AMCase mRNA in allergic rhinitis are related with the nasal symptoms score (r = 0.411, P < 0.05).. Increased expression of AMCase mRNA in nasal mucosa in allergic rhinitis model might play roles in the pathogenesis of AR, and Restrain the enzyme activity could become new treatment targets of allergic rhinitis.

Topics: Animals; Chitinases; Nasal Mucosa; Ovalbumin; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; RNA, Messenger

To investigate the influence of budesonide on animal model of minimal persistent inflammation (MPI) of allergic rhinitis in rats and to investigate the changes of interleukin-12 (IL-12) in nasal mucosa.. Sixty Sprague-Dawley (SD) rats were randomly divided into four groups: group A (allergic rhinitis group), B (experimental group), C (MPI model group) and D (bland group) respectively, with fifteen animals in each group. Rats from group A,B and C were sensitized intraperitoneally by injection of suspension of ovalbumin (OVA) and aluminum hydroxide in 0.9% physiological saline. Then, repeated local booster sensitization with different concentration of OVA suspension (1% and 0.01%) or physiological saline into the nasal cavity of those rats were performed. For group D, physiological saline was used only. From 36th day, group B were given budesonide treatment for three weeks. A, C and D group were given normal saline nasal spray. Symptoms (sneezing) of rats after antigen challenge were observed and the infiltration of eosinophils (EOS) together with the expression of intercellular adhesion molecule 1 (ICAM-1) and IL-12 in the nasal epithelial cells were also examined.. When challenged with 1% OVA, the sneezing number of rats in group B was increased markedly than that in group D (P < 0.05). However, there was no difference between group B, A and C (P > 0.05). When challenged with 0.01% OVA and given budesonide, the symptom of sneezing almost disappeared in group B just like that in group D and there was no difference between the two groups (P > 0.05). Besides, there was still more EOS infiltrated in the nasal mucosa of rats in group C than that in group D (P < 0.05). There was no expression of ICAM-1 in nasal epithelium of rats in group D, nevertheless, ICAM-1 was found mildly expressed in group C. IL-12 expression was significantly increased compared with group A and group C, and was no significantly difference compared with bland group (P > 0.05).. Budesonide significantly inhibited the late reaction of animal model of minimal persistent inflammation (MPI) of allergic rhinitis in rats and increase the expression of IL-12 in MPI model.

Topics: Allergens; Animals; Budesonide; Disease Models, Animal; Eosinophils; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-12; Leukocyte Count; Nasal Mucosa; Ovalbumin; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic

To explore the changes of microRNAs in nasal mucosa after the specific immunotherapy (SIT) for allergic rhinitis (AR) in mice.. Female BALB/c mice, 6-8 weeks of age, were randomly divided into control group, model group and treatment group. AR model were established by intraperitoneal injection and intranasal challenge of ovalbumin and SIT was performed by inguinal subcutaneous injections. AR symptom scores were documented. The eosinophils (EOS) in the nasal mucosa were measured. Ovalbumin-specific IgE (OVA-sIgE) in the serum and expression of interferon-γ and interleukin-4 in the nasal lavage were measured by enzyme-linked immunosorbent assay meanwhile the ratio of interferon-γ and interleukin-4 was calculated. The microRNAs in the nasal mucosa were preliminary screened by microRNA gene microarray. Comparing with model group, the Fold changes of microRNA of the treatment group were ≥ 2.0 and the P < 0.05. MicroRNA target genes were predicted with GeneSpring 12.5 software. We took the intersection between genes in the signal pathway which associated with immune response,inflammation and target genes. The MEV-4-6-0 and Cytoscape_v2. 8. 2. software was applied to perform the cluster analysis and target gene regulatory networks maps.. The model of AR in mice and its SIT were successful. Comparing with the model group, the Fold changes of 15 microRNAs, of which 9 microRNAs were up-regulated and 6 microRNAs were down-regulated, were ≥ 2.0 in treatment group (P < 0.05). Cluste analysis showed clearly that microRNAs in the treatment group and model group respectively aggregated in two branches. The 15 microRNAs had 5302 target genes, of which, 451 genes were related more with SIT by the intersection. One microRNA can regulate many target genes, and one gene can also be affected by many microRNAs. Their synergistic effects may be involved in the mechanism of SIT.. The expressions of microRNAs are changed in nasal mucosa after SIT for AR in mice and we can speculate that microRNAs are involved in the process of SIT for AR. Bioinformatics methods can diminish the scope of target genes of microRNAs, which will help us studying the effect of changed microRNA on its relative target genes after SIT, and make us better understanding the mechanism of the disease and its SIT.

Topics: Administration, Intranasal; Animals; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Eosinophils; Female; Immunoglobulin E; Immunotherapy; Interferon-gamma; Interleukin-4; Mice; Mice, Inbred BALB C; MicroRNAs; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic

Allergic rhinitis (AR) is a very common worldwide problem; patients display a number of symptoms, such as sneezing, nasal itching, and rhinorrhea, and their lifestyle is affected. Desloratadine is a novel, long-acting inhibitor of histamine. However, very little is known about the effect of desloratadine citrate disodium injection (DLC injection) on AR, and the underlying mechanisms are yet unexplored. Herein, we sought to explore the effects and mechanisms of actions of DLC injection in ovalbumin (OVA)-induced immune responses in a rat model of AR.. Sixty rats were subjected to immunization with OVA (intraperitoneal [i.p.]), followed by a nasal challenge with OVA. Drugs or saline were given daily for treatment. Nasal symptoms and histology of the nasal mucosa were examined. Cytokines such as interleukin (IL)-4, IL-12, interferon (IFN)-γ, adhesion molecules such as soluble vascular cell adhesion molecule 1 (sVCAM-1), and inducible nitric oxide synthase (iNOS) expression were assessed by enzyme-linked immunosorbent assay (ELISA) kit. Nitric oxide (NO) concentration was also measured by NO assay kit.. DLC treatment (intravenous [i.v.]) significantly decreased the frequency of sneezing and nasal scratching and alleviated nasal inflammation by increasing the serum levels of IFN-γ and IL-12, while lowering the expression of IL-4. Thus, DLC (i.v.) treatment led to a marked elevation in T-helper 1/T-helper 2 (Th1/Th2) ratio when administered in the AR rats. The expression of sVCAM-1, iNOS, and NO were also reversed.. DLC (i.v.), given after an allergen challenge, improved Th1 cytokines level and restrained Th2 responses alleviating the symptoms of AR. Our results indicate that DLC injection may exhibit such effects through the modulation of T-cell responses.

Topics: Allergens; Animals; Cell Adhesion Molecules; Citrates; Cytokines; Disease Models, Animal; Gene Expression Regulation; Histamine Antagonists; Humans; Immunomodulation; Loratadine; Nitric Oxide Synthase Type II; Ovalbumin; Rats; Rhinitis, Allergic; Sodium Citrate; T-Lymphocytes; Th1-Th2 Balance

Given the relationship between allergic rhinitis (AR) and asthma, it can be hypothesized that reducing upper airway inflammation by targeting oligodeoxynucleotides with CpG motifs (CpG-ODN) specifically to the upper airway via intranasal administration in a small volume (10 μL) might improve lower airway (asthma) outcomes. The goal of this study was to investigate the therapeutic efficacy of 10 μL of intranasal versus intradermal administration of CpG-ODN in suppressing lower airway inflammation and methacholine-induced airway hyperreactivity (AHR) in mice subjected to ovalbumin (OVA)-induced combined allergic rhinitis and asthma syndrome (CARAS). OVA-sensitized BALB/c mice were subjected to upper-airway intranasal OVA exposure three times per week for 3 weeks. Then, CpG-ODN was administered to a subset of these mice 1h after intranasal OVA exposure, followed by five days of OVA aerosol challenges, thereby targeting OVA to the lower airways. Immunologic variables and nasal symptoms were evaluated. The results showed that the CARAS mice exhibited significant increases in bronchoalveolar lavage fluid (BALF) and splenocytes Th2-associated cytokine production, OVA-specific serum IgE, and AHR, as well as nose and lung pathologies. Intranasal administration of CpG-ODN significantly reduced Th2-associated cytokine production, the percentage of eosinophils in the BALF, the IL-4 and IL-5 concentrations in the supernatants of cultured OVA-challenged splenic lymphocytes, the serum OVA-specific IgE levels, the peribronchial inflammation score in the lungs, and the severity of nose pathology and nasal symptoms. However, intradermal administration of CpG-ODN did not significantly reduce the aforementioned parameters. In conclusion, intranasal treatment with CpG-ODN attenuated AR and significantly alleviated lower airway inflammation and AHR in the CARAS model. CpG-ODN therapy was more effective when administered intranasally than when administered intradermally. The current study supports the development of CpG-ODN nasal spray as a novel therapeutic agent for CARAS.

Topics: Administration, Intranasal; Allergens; Animals; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Eosinophilia; Female; Immunoglobulin E; Lymphocytes; Mice, Inbred BALB C; Nasal Mucosa; Oligodeoxyribonucleotides; Ovalbumin; Rhinitis, Allergic; Spleen; Syndrome

Interleukin-23 (IL-23) and IL-17 are involved in the pathogenesis of allergic rhinitis (AR). However, the roles of IL-23 and IL-17 in ovalbumin (OVA)-induced AR remain unclear. Therefore in this study we aim to investigate the precise roles of IL-23 and IL-17 in a mouse model of OVA-induced AR. We found that during OVA-induced AR, eosinophil and goblet cells in the nose were significantly decreased in IL-23-deficient, but not in IL-17-deficient mice. However, there was no difference in the serum IgE and IgG1 levels between IL-23-deficient or IL-17-deficient and wild-type mice. Moreover, IL-4 levels in lymph node cell culture supernatants were significantly decreased in IL-23-deficient, but not IL-17-deficient, compared with wild-type mice. Furthermore, OVA-induced AR developed similarly in wild-type mice transferred with either IL-23-deficient BM cells or wild-type BM cells. These findings suggest that IL-23, but not IL-17 is crucial for the development of OVA-induced AR, and IL-23 neutralization may be a potential approach for treatment of OVA-induced AR in humans.

Topics: Animals; Bone Marrow Cells; Cell Differentiation; Disease Models, Animal; Eosinophilia; Female; Goblet Cells; Humans; Hyperplasia; Interleukin-17; Interleukin-23; Interleukin-4; Leukocytes; Mice, Inbred C57BL; Ovalbumin; Rhinitis, Allergic; Stem Cells; Th2 Cells; Up-Regulation

Mast cell (MC) degranulation is the foundation of the acute phase of allergic rhinitis (AR). Previously, downregulation of GATA binding protein 3 (GATA-3) was shown to suppress MC activation in an AR mouse model. Binding of microRNA-135a (miR-135a) to GATA-3 was also observed, and overexpression of this miRNA decreased GATA-3 mRNA and protein expression. However, the effects of miR-135a on MCs during AR are currently unknown. In the present study, we utilized a lentiviral (LV) vector to intranasally administer miR-135a to ovalbumin (OVA)-sensitized AR mice. Following miR-135a treatment, the total serum IgE concentration observed during AR was significantly reduced. In the nasal mucosa, the expression of T-box expressed in T cells (T-bet) was higher, whereas that of GATA-3 was lower in the AR mice following miRNA treatment. Notably, during AR, the ratio of type 1 T-helper cells (Th1) to type 2 (Th2) cells in the spleen is unbalanced, favoring Th2. However, administering miR-135a to the AR mice appeared to balance this ratio by increasing and decreasing the percentage of Th1 and Th2 cells, respectively. MiR-135a also appeared to strongly suppress the infiltration of eosinophils and MCs into the nasal mucosa, and it was specifically localized in the MCs, suggesting that its influence is modulated through regulation of GATA-3 in these cells. Additional work identifying the full therapeutic potential of miR-135a in the treatment of AR and diseases involving allergen-induced inflammation is warranted.

Topics: Administration, Intranasal; Allergens; Animals; Flow Cytometry; GATA3 Transcription Factor; Gene Expression; Genetic Vectors; Lentivirus; Mast Cells; Mice, Inbred BALB C; MicroRNAs; Microscopy, Confocal; Nasal Mucosa; Ovalbumin; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis, Allergic; T-Box Domain Proteins; Th1 Cells; Th2 Cells

Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway.

Topics: Animals; Anti-Allergic Agents; Cells, Cultured; Chemokine CCL2; Chemokine CCL5; Chemokines; Disease Models, Animal; Epithelial Cells; Extracellular Signal-Regulated MAP Kinases; Guinea Pigs; Histamine; Histamine H1 Antagonists; Humans; Injections; Interleukin-8; Loratadine; Nasal Lavage Fluid; Nasal Mucosa; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Signal Transduction

To investigate the effect of dxamethasone (DEX) on the expression of Tregs in allergic rhinitis (AR) mice, and explore the mechanism of glucocorticoid in the treatment of AR.. AR murine model was established by sensitization and challenge with OVA, besides intervention treatment with DEX was carried out in AR model. The behavior observation was used to evaluate the improvement effect of DEX on AR symptoms. The morphological characteristics of nasal tissues were observed by HE staining after fixation and decalcification. The mononuclear cells were obtained by grinding spleens, and the total RNA was extracted for reverse transcriptase polymerase chain reaction to investigate the level of mRNA expression of Foxp3. The changes of CD4+ Foxp3+ Tcells in spleen of mice were analyzed by flow cytometry.. BALB/c mice received OVA sensitization followed by OVA intranasal challenge, the frequencies of sneezing and nose-scratching increased significantly in AR group (44. 50 ± 5. 61 and 72. 94 ± 8. 76) compared with control group (12. 68 ± 1. 87 and 26. 76 ± .2. 89), P<0. 01; The frequencies decreased significantly in DEX group (26. 04 ± 3. 93 and 56. 79 ± 5. 64), P< 0. 05 compared with AR group. The continuity of nasal mucosa ciliated columnar epithelium in AR group was destroyed and appeared to be repaired in DEX group. Inflammatory cells infiltration was also markedly decreased by DEX treatment. The proportion of CD4+ Foxp3+ T cells in AR group (3. 89 ± 0. 39)% decreased, P<0. 01 vs control group (4. 63 ± 0. 15) %. DEX treatment induced production of Tregs (6. 89 ± 0. 49)%, P<0. 05 vs control group. DEX significantly increased the expression of Foxp3 mRNA (P<0. 05) compared with AR and control group.. DEX reduce upper airway allergic inflammation effectively, which may be mediated by promoting the expression of Foxp3 and inducing the amplification of Tregs in vivo.

Topics: Administration, Intranasal; Animals; Dexamethasone; Disease Models, Animal; Flow Cytometry; Forkhead Transcription Factors; Inflammation; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; RNA, Messenger; T-Lymphocytes, Regulatory

Mast cells are well established effector cells of type I hypersensitivity reactions such as allergic rhinitis. However, recent studies have suggested that activated mast cells enhance local immunoglobulin E (IgE) synthesis in the nasal mucosa of allergic rhinitis patients. Therefore, we hypothesized that non-immunological mast cell activators may have the potential to enhance local IgE synthesis. Here, we examined the effect of compound 48/80 (C48/80), a mast cell activator, on IgE and immunoglobulin G (IgG) synthesis. Female Balb/c mice were intranasally administered a mixture of ovalbumin (OVA) (1-10 µg/nose) and C48/80 (1-100 µg/nose) on days 0, 7, 14 and 21 and on consecutive days from day 28 to day 42. Intranasal administration of C48/80 with OVA increased serum OVA-specific IgE and IgG. Double staining with fluorescent-labeled OVA and fluorescent-labeled IgE- or IgG-specific antibody demonstrated the presence of OVA-specific IgE- or IgG-producing cells in the nasal mucosa of sensitized mice. Moreover, intranasal administration of C48/80 with OVA increased the nasal mucosal interleukin (IL)-4 level and enhanced the OVA-induced symptom of sneezing. These results suggested that simultaneous activation of mast cells with antigen exposure enhances local IgE and IgG synthesis.

Topics: Administration, Intranasal; Animals; Female; Immunoglobulin E; Immunoglobulin G; Interleukin-4; Mast Cells; Mice, Inbred BALB C; Mucous Membrane; Nasal Mucosa; Ovalbumin; p-Methoxy-N-methylphenethylamine; Rhinitis, Allergic

To investigate method established and system evaluated in the model of SD rat with AR.. To establish AR model of SD rats by ovalbumin (OVA), 20 cases of SD rats were randomly divided into two groups, namely control group (10 cases) and AR group (10 cases). AR models were sensitized and challenged by OVA. Control group were used with normal saline instead of OVA. The score of pathology and praxiology were observed when the SD rats in AR group appeared typical symptom of allergic rhinitis, and levels of IL-4, IFN-γ, IgE in the serum were examined by ELISA. According to the behavioral score, nasal histology and content of IL-4, IFN-γ, IgE of serum, Rat allergic rhinitis model were judged successfully established or not.. Behavioral scores were significantly increased in OVA-challenged rats compared with the control group, P<0.05. Nasal epithelial goblet cells, eosinophils and lymphocytes in nasal mucosa in the AR rats exhibited obvious increase relative to the control group. IL-4, IgE levels in the AR rat exhibited obvious increase relative to control group while INF-γ levels exhibited obvious reduction (P<0.05).. The allergic rhinitis models in SD rat by OVA were successfully established. The levels of IgE, INF-γ and IL-4 in Serum can be used as objective evaluation of animal models of allergic rhinitis established successfully or not.

Topics: Animals; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Eosinophils; Goblet Cells; Immunoglobulin E; Interferon-gamma; Interleukin-4; Nasal Mucosa; Ovalbumin; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic

H2-EB1 molecule which is the homolog of Human HLA-DRB1 is proposed to be associated with allergic rhinitis (AR). Construction of H2-Eb1 knockout animal models provides a tool to elucidate the role of H2-EB1 and AR pathogenesis.. To establish the H2-Eb1 knockout model and investigate the H2-EB1 functions in H2-Eb1 knockout mice as a model of AR.. The Cre/LoxP system and ES gene knockout technology were applied to create heterozygous H2-Eb1 (+/-) knockout mice and their offspring of knockout homozygous(-/-), heterozygous (+/-) and wild type (+/+) H2-Eb1 mice. After identification, offspring of heterozygous (+/-) and homozygous (-/-) H2-Eb1 knockout mice were randomly selected to establish AR models to demonstrate the role of H2-Eb1 in AR pathogenesis.. The H2-Eb1 knockout mice model was successfully established. The reproduction and feeding of the homozygous (-/-) H2-Eb1 knockout mice were successful. Compared with the control group, the serum OVA-IgE and IL-4 levels significantly increased, while IFN-γ levels significantly dropped (p<0.05) in the experimental groups. For the two experimental groups, the homozygous (-/-) mice group had lower serum OVA-IgE and IL-4 levels, and higher IFN-γ levels than their heterozygous (+/-) counterparts (p<0.05), concomitant with slighter allergic symptoms (gentle behavior and less eosinophils in nasal mucosa).. Our study demonstrated that knockout of H2-Eb1 gene could alleviate mouse AR Symptoms, indicating H2-Eb1 may play an important role in regulating Th1/Th2 balance during the pathogenesis of AR.

Topics: Allergens; Animals; Cytokines; Disease Models, Animal; Eosinophils; Female; Histocompatibility Antigens Class II; HLA-DRB1 Chains; Humans; Immunoglobulin E; Interferon-gamma; Interleukin-4; Male; Mice; Mice, 129 Strain; Mice, Knockout; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Th1-Th2 Balance; Th2 Cells

Two major distinct subsets of dendritic cells (DCs) are arranged to regulate immune responses: DEC-205+ DCs drive Th1 polarization and 33D1+ DCs establish Th2 dominancy. Th1 polarization can be achieved either by depletion of 33D1+ DCs with a 33D1-specific monoclonal antibody (mAb) or by activation of DEC-205+ DCs via intraperitoneal injection of α-galactosylceramide (α-GalCer). We studied the effect of 33D1+ DC depletion or DEC-205+ DC activation in vivo using an established mouse model of allergic rhinitis (AR).. Mice were injected intraperitoneally with OVA plus alum and challenged 4 times with daily intranasal administration of OVA. Immediately after the last challenge, allergic symptoms such as sneezing and nasal rubbing as well as the number of cells in the bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NALF) were counted. The levels of serum OVA-specific IgG1, IgG2a, and IgE were also determined by ELISA.. The allergic symptom scores were significantly decreased in 33D1+ DC-depleted or DEC-205+ DC-activated AR mice. The levels of OVA-specific IgG1, IgG2a, and IgE, and the number of NALF cells, but not BALF cells, were reduced in 33D1+ DC-depleted but not in DEC-205+ DC-activated AR mice. Moreover, the activated DEC-205+ DCs suppressed histamine release from IgE-sensitized mast cells, probably through IL-12 secretion.. The manipulation of innate DC subsets may provide a new therapeutic strategy for controlling various allergic diseases by reducing histamine release from IgE-sensitized mast cells by driving the immune response towards Th1 dominancy via activation of DEC-205+ DCs in vivo.

Topics: Alum Compounds; Animals; Bronchoalveolar Lavage Fluid; Cell Count; Cell Lineage; Dendritic Cells; Disease Models, Animal; Female; Galactosylceramides; Histamine Release; Humans; Immunoglobulin E; Immunoglobulin G; Injections, Intraperitoneal; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Primary Cell Culture; Rhinitis, Allergic; Severity of Illness Index; Sneezing; Th1 Cells; Th2 Cells

To study the role of P-JNK and P-c-Jun of JNK (c-Jun N-terminal kinase) on nasal mucosa remodeling in allergic rhinitis rats.. Sixty male Wistar rats (weighing about 200-250 g) were randomly divided into AR group (A group) and B group(control group). The rats in A group were sensitized for inducing AR by intraperitoneal injection of ovalbumin and Al(OH)₃. Rats in group A were randomized into A4, A8 and A12 group (each had 10 rats). Ovalbumin was dropped in each nasal cavity of every rat for 4,8,12 weeks, respectively. Rats in group B were sensitized by saline instead of OVA, and were also divided into B4, B8 and B12 group. Each group had 10 rats. Pathological changes of nasal mucosa in each period were observed by hematoxylin and eosin stain dyeing. The phosphorylation of JNK and c-Jun were tested by immunohistochemistry.. In A8 group, mucosal congestion and edema thickening with inflammatory cells infiltration of eosinophils were observed in the eighth week, and the inflammatory changes were significantly increased as time went on. The mean absorbance values of P-JNK and P-c-Jun in A group were significantly higher than those in the corresponding B group (all P < 0.01). Moreover, the mean absorbance values of A12 group were significantly higher than A4 group and A8 group (all P < 0.01 ).. The expression of P-JNK and P-c-Jun in the process of nasal mucosa remodeling in allergic rhinitis rats were increased, which suggested that P-JNK and P-c-Jun played important roles in nasal mucosa remodeling of the allergic rhinitis rats.

Topics: Airway Remodeling; Animals; Disease Models, Animal; Eosinophils; Injections, Intraperitoneal; JNK Mitogen-Activated Protein Kinases; Male; Nasal Mucosa; Ovalbumin; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Rhinitis, Allergic; Signal Transduction

To investigate 18β-sodium glycyrrhetinic acid impact on nasal mucosa epithelial cilia in rat models of allergic rhinitis (AR).. AR models were established by ovalbumin-induction. Wister rats were randomly divided into groups as normal group, model group, budesonide (0.2 mg/kg) group and sodium glycyrrhetinic acid (20 mg/kg and 40 mg/kg) group after the success of AR models. At 2 weeks and 4 weeks after treatment, the behavioral changes of rats were observed and recorded, and nasal septum mucosae were collected after 2 week and 4 week intervention, and the morphological changes of nasal mucosae were observed by electron microscope.. Model group developed typical AR symptoms, the total score in all animals was > 5. With budesonide and sodium glycyrrhetinic acid treatment, the AR symptoms were relieved, and the total scores were reduced significantly (P < 0.01). Compared with the model group: after 2 weeks' intervention, thick mucous secretions on the top of columnar epithelium cilia in rat nasal mucosa was significantly reduced, and cilia adhesion, lodging, shedding were relieved in budesonide group and sodium glycyrrhetinic acid group, the relieve in budesonide group was slightly better than that in sodium glycyrrhetinic acid group; after 4 week intervention, Cilia adhesion, lodging, shedding were completely vanished, and the cilia were ranged in regular direction in budesonide group and sodium glycyrrhetinic acid group. Cilia in sodium glycyrrhetinic acid (20 mg/kg) group was more orderly, smooth than that in budesonide group and sodium glycyrrhetinic acid group (40 mg/kg), and the condition of cilia in sodium glycyrrhetinic acid group (20 mg/kg) was similar to the normal group.. 18β-sodium glycyrrhetinic acid is effective to restrain the pathological changes of nasal mucosa cilia in rat models of AR.

Topics: Animals; Budesonide; Cilia; Disease Models, Animal; Glycyrrhetinic Acid; Nasal Mucosa; Ovalbumin; Random Allocation; Rats; Rhinitis, Allergic

In this study, we investigated the effects of Naju Jjok (Polygonum tinctorium Lour., NJJ) on interleukin (IL)-32 and thymic stromal lymphopoietin (TSLP) levels associated with allergic rhinitis (AR). Using female BALB/c mice, we created an animal model of ovalbumin (OVA)-induced AR. Prior to the callenge with OVA, the mice were administered, either nasally or orally with NJJ. In addition, we also used the eosinophilic cells line, Eol-1, stimulated with granulocyte‑macrophage colony-stimulation factor (GM-CSF). The mRNA and protein levels of inflammatory cytokines and markers [interleukin (IL)-32, IL-4, macrophage-inflammatory protein-2 (MIP-2), intercellular adhesion molecule-1 (ICAM-1), and cyclooxygenase-2 (COX-2)] were measured by RT-PCR and western blot analysis, respectively and serum levels were measured by ELISA. The increased levels of IL-32 in the mice with AR and in the stimulated eosinophilic cell line, Eol-1, were significantly reduced by NJJ. TSLP levels were also decreased following the oral administration of NJJ. Mice orally administered NJJ showed markedly alleviated clinical symptoms, such as a reduced number of nasal rubs, decreased spleen weight, decreased serum immunoglobulin E (IgE) levels and decreased serum histamine levels. The oral administration of NJJ significantly decreased the IL-4 levels, while increasing the interferon-γ levels in the spleen. The increased number of eosinophils and mast cells infiltrating the nasal mucosal tissue of the mice with AR were decreased following the oral administration of NJJ. NJJ effectively attenuated caspase-1 activity in the mice with AR and in the stimulated Eol-1 cells. The oral administration of NJJ significantly reduced the levels of inflammatory markers, such as MIP-2, ICAM-1 and COX-2. Furthermore, the intranasal administration of NJJ significantly reduced the early phase response to allergen exposure, such as nasal rubs, IgE production and histamine release, as well as the late phase responses, such as the expression of inflammatory markers. In conclusion, these data demonstrate that NJJ may play a regulatory role in nasal inflammation.

Topics: Administration, Oral; Animals; Caspase 1; Cell Line; Chemokine CXCL2; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Eosinophils; Female; Histamine; Humans; Immunoglobulin E; Intercellular Adhesion Molecule-1; Interferon-gamma; Interleukins; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Polygonum; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Spleen; Thymic Stromal Lymphopoietin

Almost a quarter of the world population suffers from IgE-mediated allergies. T cells and IgG-producing B cells can produce protection, but treatment for disease is laborious with unsatisfactory patient compliance.. We sought to identify whether paediatric allergy vaccines affected later allergen sensitization and onset of disease when used prophylactically.. A murine model of anaphylaxis was applied. Mice were first immunized with monovalent or multivalent allergy vaccines that also contained aluminium hydroxide and CpG oligodeoxynucleotide as adjuvants. Later, the mice were sensitized by multiple low-dose injections of aluminium-adsorbed allergen. After a dormant period, the mice were challenged systemically with high-dose allergen, and the clinical signs of anaphylaxis were recorded. Throughout the immunization and sensitization periods, blood was collected for serological testing.. Immunization with allergy vaccines produced antigen-specific protection against sensitization as measured by systemic anaphylaxis in mice. The long-term effect was observed both after juvenile (5-6 weeks) and neonatal (7 days) vaccination. Monovalent and pentavalent vaccines were protective to a similar level. Protection was associated with increased secretion of IgG2a and production of IFN-γ. Protection could also be transferred to sensitized mice via serum or via CD25-positive CD4 T cells.. Prophylactic and multivalent allergy vaccines in juvenile and neonatal mice protected against later sensitization and anaphylaxis. Such treatment may provide a rational measure for future management of allergen-related diseases and their strong socio-economic impact on daily life.

Topics: Adoptive Transfer; Allergens; Anaphylaxis; Animals; Cross Protection; Disease Models, Animal; Female; Humans; Immunization Schedule; Immunoglobulin E; Immunoglobulin G; Mice; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Vaccines

Anticholinergic drugs or vidian neurectomy can alleviate the symptoms of allergic rhinitis.. To show that inhibition of the cholinergic nerve influences the balance of T-helper type 1 and 2 cells in allergic rhinitis mice.. Twenty-four mice were randomly allocated to 1 of 4 groups: control, model, model with ipratropium bromide treatment, and model with 6-hydroxydopamine treatment. Allergic model-treated mice were sensitized with ovalbumin. Evaluation of allergic symptoms was recorded according to a symptom score. Ovalbumin serum IgE was measured by enzyme-linked immunosorbent assay. Expression of interleukin-4, interferon-γ, forkhead box P3, substance P, and vasoactive intestinal peptides was detected by immunohistochemistry and imaging analysis.. Symptoms in allergic mice were significantly alleviated by ipratropium bromide. Ovalbumin serum IgE and eosinophils of nasal mucosa were significantly decreased. Interleukin-4 expression level was significantly higher in the allergic model group than in the control group and significantly decreased by ipratropium bromide (P < .05). In contrast, the expression of forkhead box P3 was lower in the allergic model group than in the control group and increased with treatment by ipratropium bromide (P < .05). Conversely, interferon-γ expression was not changed by anticholinergic treatment in the nasal mucosa of allergic mice. Expression of substance P and vasoactive intestinal peptide was significantly increased in allergic mice and decreased by ipratropium bromide. Sympathetic denervation did not change the expression of interleukin-4, interferon-γ, forkhead box P3, substance P, and vasoactive intestinal peptide.. inhibition of the cholinergic nerve not only alleviated symptoms of allergic rhinitis by inhibiting the impulse of the parasympathetic nerve but also modulated the T-helper type 2-predominant immune reaction, expression of neuropeptides, and related inflammation factors.

Topics: Adrenergic Agents; Animals; Cholinergic Antagonists; Cholinergic Neurons; Disease Models, Animal; Eosinophils; Female; Forkhead Transcription Factors; Gene Expression; Immunoglobulin E; Interferon-gamma; Interleukin-4; Ipratropium; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Oxidopamine; Parasympathetic Nervous System; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Substance P; Th1 Cells; Th1-Th2 Balance; Th2 Cells; Vasoactive Intestinal Peptide

Fab fragments (Fabs) have the ability to bind to specific antigens but lack the Fc portion for binding to receptors on immune and inflammatory cells that play a critical role in allergic diseases. In the present study, we investigated whether Fabs of an allergen-specific IgG1 monoclonal antibody (mAb) inhibited allergic rhinitis in mice. BALB/c mice sensitized by intraperitoneal injections of ovalbumin (OVA) plus alum on days 0 and 14 were intranasally challenged with OVA on days 28-30, and 35. Fabs prepared by the digestion of an anti-OVA IgG1 mAb (O1-10) with papain were also intranasally administered 15min before each OVA challenge. The results showed that treatment with O1-10 Fabs significantly suppressed the sneezing frequency, associated with decrease of OVA-specific IgE in the serum and infiltration by mast cells in the nasal mucosa seen following the fourth antigenic challenge; additionally, the level of mouse mast cell protease-1, a marker of mast cell activation, in serum was decreased. Furthermore, infiltration of eosinophils and goblet cell hyperplasia in the nasal mucosa at the fourth challenge were inhibited by treatment with O1-10 Fabs. In conclusion, these results suggest that intranasal exposure to Fabs of a pathogenic antigen-specific IgG1 mAb may be effective in regulating allergic rhinitis through allergen capture by Fabs in the nasal mucosa before the interaction of the intact antibody and allergen.

Topics: Administration, Intranasal; Allergens; Animals; Chemokine CCL2; Disease Models, Animal; Immunoglobulin E; Immunoglobulin Fab Fragments; Immunoglobulin G; Immunomodulation; Male; Mast Cells; Mice; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic

This study evaluated different dosage forms of aluminum adjuvant in generating allergic rhinitis animal models. Forty female BALB/c mice were assigned to four groups, including three dosage forms of aluminum adjuvant [powder, gel, and hydrosolvent of aluminum hydroxide, Al(OH)3] mixed with ovalbumin to simulate the symptoms of allergic rhinitis and one control group. Although the aluminum adjuvants were in different dosage forms, the content was 5 mg after conversion in all groups. The fourth group was given normal saline instead as a control. Mice of the powder group displayed typical symptoms of allergic rhinitis. We also found discrete eosinophils in the nasal mucosa of mice from the hydrosolvent group; however, no eosinophils were found in the gel group. These two groups both displayed cytotoxic symptoms and foreign body granuloma. Aluminum adjuvant used in producing animal models can induce foreign body granuloma and other untoward reactions, which are associated with the dosage level and form.

Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Animals; Disease Models, Animal; Eosinophils; Female; Gels; Granuloma, Foreign-Body; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Powders; Rhinitis, Allergic

Bee venom (BV) has been used as an anti-inflammatory and immune modulating agent in Oriental medicine. This study used a mouse model to investigate the anti-allergic effect of BV, which is used in the treatment of various inflammatory diseases in traditional medicine. BV was obtained from the National Institute of Agricultural Science and Technology of Korea. Female BALB/C mice were sensitized by intraperitoneal injection of ovalbumin (OVA). BV was administered nasally prior to the intranasal instillation of OVA. Allergic behavior, serum OVA-specific immunoglobulin E (IgE), interleukin (IL)-4, IL-10, and interferon-gamma (INF-γ) levels in nasal lavage fluid were measured. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate histological change. BV attenuated nasal symptoms and inhibited the production of OVA-specific IgE and IL-4 in sensitized mice. The degree of inflammatory cell infiltration and goblet cell hyperplasia was attenuated by BV. Thus, BV effectively reduced allergic inflammation in a mouse model of allergic rhinitis, suggesting its potential as a useful therapeutic agent to treat allergic rhinitis.

Topics: Allergens; Animals; Anti-Allergic Agents; Bee Venoms; Cytokines; Disease Models, Animal; Female; Immunoglobulin E; Mice, Inbred BALB C; Mucins; Nasal Lavage Fluid; Nasal Mucosa; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Transcription Factor AP-1

To evaluate the antiallergic effects of oral benzaldehyde in a murine model of allergic asthma and rhinitis, we divided 20 female BALB/c mice aged 8-10 weeks into nonallergic (intraperitoneally sensitized and intranasally challenged to normal saline), allergic (intraperitoneally sensitized and intranasally challenged to ovalbumin), and 200- and 400-mg/kg benzaldehyde (allergic but treated) groups. The number of nose-scratching events in 10 min, levels of total and ovalbumin-specific IgE in serum, differential counts of inflammatory cells in bronchoalveolar lavage (BAL) fluid, titers of Th2 cytokines (IL-4, IL-5, IL-13) in BAL fluid, histopathologic findings of lung and nasal tissues, and expressions of proteins involved in apoptosis (Bcl-2, Bax, caspase-3), inflammation (COX-2), antioxidation (extracellular SOD, HO-1), and hypoxia (HIF-1α, VEGF) in lung tissue were evaluated. The treated mice had significantly fewer nose-scratching events, less inflammatory cell infiltration in lung and nasal tissues, and lower HIF-1α and VEGF expressions in lung tissue than the allergic group. The number of eosinophils and neutrophils and Th2 cytokine titers in BAL fluid significantly decreased after the treatment (P<0.05). These results imply that oral benzaldehyde exerts antiallergic effects in murine allergic asthma and rhinitis, possibly through inhibition of HIF-1α and VEGF.

Topics: Animals; Anti-Allergic Agents; Asthma; Benzaldehydes; Bronchoalveolar Lavage Fluid; Cell Count; Cytokines; Disease Models, Animal; Female; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoglobulin E; Lung; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Vascular Endothelial Growth Factor A

Interleukin (IL)-25, a cytokine of IL-17 family, can activate p38 Mitogen-Activated Protein kinases(MAPK) and Nuclear Factor(NF)-κB pathways to propagate Th2 responses. The allergic rhinitis mouse model was established by stimulating BALB/c mouse with ovalbumin (OVA). Then we detected expression of IL-25 and downstream p38MAPK and NF-κB. The expression of IL-25, p38MAPK and NF-κB were detected in the OVA-induced allergic rhinitis mouse model. The allergic parameters, such as allergic symptoms, serum OVA-specific immunoglobulin E (IgE) levels and eosinophil infiltration in the nasal mucosa were compared between OVA group and control group. OVA-induced mice displayed significantly higher allergic responses compared with the saline control group. OVA induced mice demonstrated more allergic symptoms, higher serum OVA-specific IgE levels and eosinophil infiltrations. The increased expression of IL-25, p38MAPK and NF-κB immunoreactivity were detected in epidermal cells in the OVA group. The mRNA measurement of IL-25, p38MAPK and NF-κB showed the same result. IL-25 enhances the OVA-induced allergic rhinitis by activating p38MAPK and NF-κB pathways.

Topics: Animals; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Immunoglobulin E; Interleukins; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; p38 Mitogen-Activated Protein Kinases; Rhinitis, Allergic; Signal Transduction

Allergic rhinitis (AR) is an allergic inflammation of the nasal airways. The prevalence of AR is increasing worldwide. We investigated whether Hyeonggaeyeongyo-tang (HYT) is effective to suppress the progression of AR induced by ovalbumin (OVA). Male BALB/c mice were used for this study. Allergic rhinitis was induced by OVA. Treatment with HYT was assessed to study the effect of HYT on allergic rhinitis in mice. Histological analysis, immunohistochemistry, multiplex cytokine assay, blood analysis, and cell viability assay were performed to verify inhibitory effect of HYT on allergic rhinitis. HYT did not show any toxicity maintaining body weight. Food intake was steady without variation in mice. HYT reduced infiltration of inflammatory cells and mast cells into nasal cavity. HYT reduced the levels of cytokines and leukocytes in the blood. HYT decreased the splenocyte cell viability. Antihistamines and steroids are the most common medications used to treat allergic rhinitis. However, long-term use of drug generates resistance or side effects requiring the development of new drug. Our present study clearly demonstrates that HYT suppresses the progression of allergic rhinitis induced by OVA. This suggests that HYT might be a useful drug for the treatment of allergic rhinitis.

Topics: Animals; Anti-Allergic Agents; Body Weight; CD4-Positive T-Lymphocytes; Cell Survival; Cells, Cultured; Eating; Immunohistochemistry; Leukocytes; Mast Cells; Mice; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic

The precise pathogenesis of allergic rhinitis (AR) remains unclear and AR is less easily cured. Recent evidence has suggested that calcium-activated K+ channel-3.1(KCa3.1) is implicated in the immune response of allergic and inflammatory diseases and TRAM-34 is a selective KCa3.1 blocker. However, little is known about its role in AR. We aimed to investigate the effect of TRAM-34 in a mouse model of AR induced by ovalbumin (OVA). The BALB/c mice were divided into six groups: untreated AR group, 200 μg TRAM-34 treated AR group, 400 μg TRAM-34 treated AR group, 200 μg TRAM-34 treated normal group, 400 μg TRAM-34 treated normal group and untreated normal control group. Histopathological characteristics were assessed by HE staining. KCa3.1 protein expression was investigated by immunohistochemistry and western blotting method, and mRNA expression of KCa3.1, stromal interaction molecule1 (STIM1) and Orai1 in nasal tissues were assessed by real-time PCR. Furthermore, concentrations of OVA-specific IgE, ECP, IL-4, IL-5, IL-17 and IL-1β in nasal lavage fluid (NLF) were analyzed by enzyme-linked immunosorbent assay (ELISA). Results showed that TRAM-34 administration into the nostril attenuated sneezing, nasal rubbing, epithelial cell proliferation, eosinophil infiltration and inhibited nasal mucosa KCa3.1, STIM1 and Orai1 expression in TRAM-34 treated mice compared with untreated AR mice and suppressed inflammatory cytokines in the NLF of TRAM-34 treated groups compared with untreated AR mice. In conclusion, TRAM-34 could effectively alleviate murine allergic rhinitis by suppressing KCa3.1 and leads to reduction of K+ efflux and Ca2 + influx, leading to inflammation reduction and allergic responses attenuation.

Topics: Administration, Intranasal; Animals; Blotting, Western; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Immunoglobulin E; Intermediate-Conductance Calcium-Activated Potassium Channels; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Potassium Channel Blockers; Pyrazoles; Rhinitis, Allergic

To observe 18β-glycyrrhetinic acid (GA) impact on ultrastructure of tight junctions (TJs) of nasal mucosa epithelial cells in rats models of allergic rhinitis (AR).. Ninety-six Wistar rats were randomly divided into control group, model group, loratadine group, and 18β-glycyrrhetinic acid group, and each group had 24 rats. Ovalbumin was used to establish a rat AR model. The behavioral changes and the tight junctions of nasal epithelial were observed and compared in different groups after 2,4,6 and 10 weeks intervention.. The length of TJs in allergic rhinitis model became shorter, electron-high-density plasma membrane became thicker, number of the integration loci reduced and gap of TJs widened or even ruptured. With the consistent effect of allergens,the changes of TJs in the model group aggravated gradually,and the changes of ultrastructure of TJs in 18β-glycyrrhetinic acid group was relieved apparently compared to model group and even were close to the control model with time.. 18β-glycyrrhetinic acid can recover the ultrastructure of the tight junctions of AR rat nasal epithelial cells.

Topics: Animals; Cell Count; Epithelial Cells; Glycyrrhetinic Acid; Nasal Mucosa; Ovalbumin; Rats; Rats, Wistar; Rhinitis, Allergic; Tight Junctions

This study was designed to find out the impact of micro-ecological environment on the incidence of allergic rhinitis after developing a model of allergic rhinitis on mice.. Sixty mice were randomly divided into GF group (n=30) and SPF group (n=30). Mice of GF group were fed in the germ-free environment and mice of SPF group were fed in the specific pathogen-free environment. Then each group were randomly divided into model group (20 mice) and control group (10 mice). Establish allergic rhinitis model in the mice of model group using ovalbumin (OVA) at the age of 6 weeks, observe and score the corresponding symptoms and signs that could been induced. Stain with hematoxylin eosin (HE) staining method for nasal mucosa to observe the morphological changes. Using enzyme linked immunosorbent assay to detect the concentration of IgE, IFN-γ and IL-4 in the peripheral blood serum.. The chi square test showed that the incidence of allergic rhinithis in the mice of GF group was significantly higher than that in the SPF group (P< 0. 05). HE staining showed that the nasal mucosas of allergic rhinitis positive reaction mice were highly congestive and edematous and had a large number of inflammatory cell infiltration, while there was no abnormal morphology of nasal mucosas in mice with no allergic rhinitis reaction. EOS counting displayed that the number of eosinophilic cells in nasal mucosa of positive allergic rhinitis reaction mice was increased significantly. The concentration of IgE and IL-4 in the serum of positive allergic rhinitis reaction mice was highly increased (P <0. 05), and IFN-γ was significantly decreased (P< 0.05).. The difference of micro-ecological environment may play a key role in the occurrence of allergic rhinitis in mice.

Topics: Animals; Disease Models, Animal; Environment; Incidence; Interleukin-4; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis; Rhinitis, Allergic

KOB03 is a polyherbal medicine derived from an oriental prescription traditionally used to treat allergic diseases. In the present study, we compared the efficacy of KOB03 with modern drugs such as ketotifen and montelukast in an experimental mouse model of allergic rhinitis (AR). Ketotifen is a H1 receptor antagonist and montelukast is a leukotriene receptor antagonist. Mice were treated with KOB03, ketotifen or montelukast in an established AR mouse model using ovalbumin (OVA)-sensitized/challenged BALB/c mice. The treatment of KOB03 had inhibitory effects on symptom scores, serum levels of OVA-specific IgE, histamine, leukotriene C4, IL-4, TNF-α, and IL-1β in AR mice, and the histolopathological changes of nasal mucosa with mucin release and inflammation. AR mice treated with KOB03 had significantly lower serum levels of OVA-specific IgE, LTC4, IL-4, and IL-1β than mice treated with ketotifen, whereas they only had significantly lower serum levels of OVA-specific IgE and IL-4 than those treated with montelukast. In addition, the histolopathological changes of nasal mucosa with eosinophil infiltration were significantly lower in the KOB03-treated mice than those in the ketotifen and montelukast-treated group. These results suggest that KOB03 has therapeutic potential for treating AR like other modern medicines.

Topics: Acetates; Animals; Anti-Allergic Agents; Antigens; Cyclopropanes; Cytokines; Disease Models, Animal; Histamine H1 Antagonists; Immunoglobulin E; Ketotifen; Leukotriene Antagonists; Leukotriene C4; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Plant Extracts; Quinolines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Sulfides

In the present experiments, the possible role of curcumin in ovalbumin induced allergic rhinitis in guinea pig model was investigated. Various allergic rhinitis symptoms viz sneezing, rubbing frequencies, lacrimation and nasal congestion at various humidity conditions as well as on repeated sensitization were studied. The biochemical changes like serum IgE, IL-4 and nitric oxide (NO) in nasal lavage and eosinophil peroxidase activity in nasal homogenates were determined in allergic rhinitis. Curcumin treatment significantly reduced the symptoms (sneezing, rubbing frequencies, lacrimation and nasal congestion) and improved the histopathological alterations (reduction in inflammatory cells infiltration) of nasal mucosa in allergic rhinitis. Furthermore, curcumin treatment prevented significantly elevation of serum IgE, IL-4, NO in nasal lavage and eosinophil peroxidase in nasal homogenate. In the present experimental findings, we suggest that curcumin is a promising anti-allergic agent that may be useful in the clinical management of allergic rhinitis.

Topics: Acetates; Animals; Cromolyn Sodium; Curcumin; Cyclopropanes; Dose-Response Relationship, Drug; Eosinophil Peroxidase; Female; Gene Expression Regulation; Guinea Pigs; Humidity; Interleukin-4; Male; Nitric Oxide; Ovalbumin; Quinolines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Sulfides

Recent epidemiological studies have suggested a positive link between atopy morbidity and exposure to phthalate esters, which are environmental chemicals mainly involved in house dust. Nevertheless, experimental studies applying several allergic in vivo models (in addition to epidemiological studies) are needed to prove the precise correlation between phthalates and facilitation of the allergic response/pathophysiology. Among the phthalate esters, di-(2-ethylhexyl) phthalate (DEHP) has been widely used in flexible polyvinyl chloride products, including vinyl flooring and wall covering, and has been widely suggested to have immunomodulating potential. In the present study, we examined the effects of airway exposure to DEHP on allergen (ovalbumin: OVA)-induced rhinitis in mice. The repeated administration of OVA via an intranasal route induced nasal inflammation characterized by the infiltration of granulocytes (neutrophils and eosinophils) into the nasal cavity. In this experimental setting, DEHP did not exaggerate OVA-related inflammatory pathology. However, local (nasal) IL-13 levels were significantly higher in mice treated with allergen plus DEHP than with allergen alone. Taken together, phthalate esters including DEHP have the potential to exacerbate the allergic milieu in the nasal system, as well as dermal and respiratory systems.

Topics: Air Pollutants; Animals; Cytokines; Diethylhexyl Phthalate; Female; Inhalation Exposure; Leukocyte Count; Mice; Mice, Inbred BALB C; Nasal Cavity; Nasal Lavage Fluid; Neutrophil Infiltration; Neutrophils; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

Allergen-specific immunotherapy (ASIT) the only disease-modifying treatment for IgE-mediated allergies is characterized with long treatment duration and high risk of side effects. We investigated the safety, immunogenicity and efficacy of a novel ASIT, called DermAll, in an experimental allergic rhinitis model. We designed and characterized DermAll-OVA, a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin (OVA) as model allergen. DermAll-OVA was administered topically with DermaPrep device to target Langerhans cells. To detect the clinical efficacy of DermAll ASIT we quantified the nasal symptoms and characterized the immunomodulatory activity of DermAll ASIT by measuring cytokine secretion after OVA-stimulation of splenocytes and antibodies from the sera. In allergic mice DermAll ASIT was as safe as Placebo, balanced the allergen-induced pathogenic TH2-polarized immune responses, and decreased the clinical symptoms by 52% [32%, 70%] compared to Placebo. These studies suggest that DermAll ASIT is safe and should significantly improve the immunopathology and symptoms of allergic diseases.. A novel allergen-specific immunotherapy for IgE-mediated allergies is presented in this paper, using an experimental allergic rhinitis model and a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin as model allergen. Over 50% reduction of symptoms was found as the immune system's balance was favorably altered toward more TH2-polarized immune responses.

Topics: Administration, Topical; Allergens; Animals; Cytokines; Female; Immunization; Immunoglobulin E; Langerhans Cells; Mice; Mice, Inbred BALB C; Nanomedicine; Ovalbumin; Plasmids; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Th2 Cells; Vaccines, DNA

To investigate the method of development of allergic airway disease model in mice.. Ten BALB/c mice were devided into the model group and the control group. Each group contained 5 mice. Ovalbumin (OVA) was used as allergen. OVA was emulsified with aluminum hydroxide and injected intraperitoneally for sensitization. Afterwards the mice from model group were challenged with aerosolized 5% OVA and subsequently instilled with OVA intranasally. For the blank control group the mice were sensitized and challenged with phosphate buffer saline (PBS). After final challenge, the nasal symptoms were scored, and mice were sacrificed for evaluation of eosinophilia of nasal septum, peribronchial inflammation and goblet cell hyperplasia. Mice serum was collected for measurement of OVA-specific IgE concentration, and levels of IL-4 and IL-5 from bronchoalveolar fluids were also tested.. Compared with blank control mice, mice from model group displayed typical sneezing and nasal scratching symptoms. The histopathological changes, such as eosinophilia of nasal septum mucosa, infiltration of peribronchial inflammatory cells and hyperplasia of goblet cells were successfully induced by OVA sensitization and challenge. Moreover, mice in model group showed higher level of OVA-specific IgE in serum and IL-4 and IL-5 cytokines in bronchoalveolar fluids[mice from model group: IgE (1237.00 ± 153.20) pg/ml, IL-4 (46.50 ± 10.15) pg/ml, IL-5 (50.81 ± 11.41) pg/ml; mice from control group: IgE (191.90 ± 43.20) pg/ml, IL-4 (7.96 ± 1.80) pg/ml, IL-5 (7.53 ± 2.23) pg/ml;t value were 6.569, 3.738 and 3.724, respectively, all P < 0.05].. The method using OVA as allergen could effectively develop a mouse model of allergic airway disease which could be used for pathogenesis study and drug effect evaluation.

Topics: Allergens; Animals; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Eosinophilia; Immunoglobulin E; Interleukin-4; Interleukin-5; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

Interleukin-23 (IL-23) and IL-17 may be involved in the pathogenesis of allergic rhinitis (AR). However, a differentiation of the role of IL-23 and IL-17 has not been performed yet.. The aim of this study was therefore to investigate the immunomodulatory effects of IL-23 and IL-17, using a mouse model of AR.. Anti-IL-23p19 and anti-IL-17 Abs were administrated intranasally during rechallenge in ovalbumin (OVA)-induced AR in BALB/c mice. Immunomodulatory effects were evaluated by measuring nasal rubbing and sneezing occurrences, serum OVA-specific antibodies, Th2 responses (i.e. expression of IL-4, IL-5, IL-13 and IFN-γ genes in nasal mucosa, IL-4(+) CD4(+) T cells percentages in superficial cervical lymph nodes (LNs) and IL-4 production in LNs stimulated with OVA in vitro), and neutrophil, eosinophil and mast cell recruitment into the nasal mucosa.. The effect of IL-17 antagonism was limited to attenuating the Th2 responses and neutrophil and eosinophil infiltration. In contrast, treatment with anti-IL-23p19 Abs markedly reduced nasal rubbing and sneezing events, Th2 responses, serum OVA-specific IgE and IgG1 levels, as well as mucosal neutrophil, eosinophil and mast cell infiltration.. IL-17 and IL-23 may play a pathogenic role in an established AR mouse model; with a more pronounced contribution of IL-23 than IL-17.

Topics: Animals; Antibodies, Monoclonal; Disease Models, Animal; Immunoglobulin E; Immunoglobulin G; Immunologic Factors; Immunomodulation; Interleukin-17; Interleukin-23; Interleukin-23 Subunit p19; Male; Mast Cells; Mice; Neutrophil Infiltration; Neutrophils; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Th2 Cells

This study is aimed at exploring the role of neurokinin-1 receptor (NK-1R) in the development of allergic rhinitis (AR) in rats.. Sprague-Dawley rats were sensitized and challenged with ovalbumin to induce AR. The rats were treated intranasally with saline, control, or NK-1R-specific small interfering RNA (siRNA) before and during the challenge period. The numbers of sneezes and nose rubs and amount of nasal secretion in individual rats were measured. The levels of NK-1R expression in the nasal mucosal tissues after the last challenge were determined. The numbers of eosinophils in the collected nasal lavage fluid and the levels of serum interleukin (IL)-5 in individual rats were determined.. The levels of NK-1R expression in the nasal mucosal tissues of the AR rats that had been treated with saline or control siRNA were significantly higher than those in the healthy controls and the rats treated with NK-1R-specific siRNA, demonstrating NK-1R silencing. Furthermore, knockdown of NK-1R expression significantly reduced the amounts of sneezing, nose rubbing, and nasal secretions in AR rats. Knockdown of NK-1R expression also significantly eliminated eosinophil infiltration in the nasal tissues and reduced the levels of serum IL-5 in rats.. Knockdown of NK-1R expression decreased allergic inflammation in nasal mucosal tissues and alleviated the allergic rhinitis symptoms, suggesting that NK-1R may be a critical mediator of the development of AR.

Topics: Allergens; Animals; Eosinophils; Gene Knockdown Techniques; Interleukin-5; Leukocyte Count; Male; Nasal Lavage Fluid; Ovalbumin; Rats; Rats, Sprague-Dawley; Receptors, Neurokinin-1; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; RNA, Small Interfering

We describe a method for allergic rhinitis (AR) induction in mice. Methodology involves nasal infusions of small volumes of ovalbumin for both initial sensitization and challenges. The latter are frequent and carried out over several weeks. This methodology more closely resembles natural AR induction than does the common use of systemic sensitization, often with adjuvants, followed by nasal challenges with relatively large allergen volumes. Also described are methodologies for collection of cardiac blood and perfusion for preparation of histological samples, both essential in verifying AR induction in individual animals.

Topics: Allergens; Animals; Disease Models, Animal; Mice; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

Kaempferol (KP) is a major compound of Naju Jjok (Polygonum tinctorium Lour.). The effect of KP on allergic rhinitis (AR) has not been elucidated. Here, we report the effects and mechanisms of KP on new and predominant mediators of AR using an eosinophil cell line, Eol-1 and an ovalbumin (OVA)-induced AR mouse model. KP significantly inhibited the production of interleukin (IL)-32 and IL-8 and activation of caspase-1 in Eol-1 cells. Allergic symptoms and predominant mediators (IgE and histamine) in the KP-administered group were significantly lower than in the AR group. The levels of interferon-γ were enhanced while the levels of IL-4 were reduced in the KP group. KP significantly reduced the levels of IL-32 and thymic stromal lymphopoietin (TSLP) compared with the AR mice. KP reduced the levels of inflammation-related proteins. In the KP-administered groups, the infiltrations of eosinophils and mast cells increased by OVA were decreased. In addition, KP significantly reduced caspase-1 activity in nasal mucosa tissue of AR mice. Our findings indicate that KP has an anti-allergic effect through the regulation of the production of IL-32 and TSLP and caspase-1 activity in allergic diseases including AR.

Topics: Animals; Anti-Allergic Agents; Caspase 1; Cell Line; Cytokines; Disease Models, Animal; Enzyme Activation; Eosinophils; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Histamine; Humans; Immunoglobulin E; Interleukin-4; Interleukin-8; Interleukins; Kaempferols; Mast Cells; Mice; Mice, Inbred BALB C; Organ Size; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Spleen; Thymic Stromal Lymphopoietin

Lactoferrin (LF) can downregulate allergic airway inflammation in asthma. However, the in vivo effect of exogenous LF on allergic rhinitis (AR), a disease attributed to airway inflammation, has yet to be determined. We investigated the effect of intranasal administration recombinant human (rh) LF and its underlying mechanisms on AR in BALB/c mice. Multiple parameters of allergic responses were evaluated to determine the effect of rhLF. We found that the number of eosinophils and goblet cells, as well as mRNA and protein expression of type 2 helper T (Th2), Th17 and regulatory T (Treg) cells in the nasal cavity, was significantly upregulated in AR mice compared with the controls, Conversely, administration of rhLF prior to or after intranasal ovalbumin challenge markedly downregulated these same parameters. Th1-specific mRNA and protein expression in the nasal cavity of the controls was not different from that in AR mice, but expression significantly increased with rhLF treatment. The mRNA and protein expression of endogenous LF in the nasal cavity was significantly downregulated in AR mice compared with the controls. However, after rhLF treatment, endogenous LF mRNA and protein expression was significantly upregulated. Exogenous rhLF inhibited allergic inflammation in AR mice, most likely by promoting the endogenous LF expression and skewing T cells to a Th1, but not a Th2 and Th17 phenotype in the nasal mucosa. Our findings suggest that rhLF treatment may be a novel therapeutic approach for prevention and treatment AR.

Topics: Administration, Intranasal; Animals; Cytokines; Disease Models, Animal; Eosinophils; Goblet Cells; Inflammation; Lactoferrin; Lymphocyte Count; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; RNA, Messenger; T-Lymphocytes, Regulatory; Th1 Cells; Th17 Cells; Th2 Cells

The aim of this study was to investigate the anti-allergic effects of lysozyme/heat-treated Enterococcus faecalis FK-23 (LFK) and heat-treated Enterococcus faecium sp. TN-3 (TN) on experimental allergic rhinitis (AR).. A total of twenty-four BALB/c mice were divided into four groups randomly: (1) positive control group, (2) LFK-fed group, (3) TN-fed group, and (4) negative control group. To establish the murine AR model, intraperitoneal injection and nasal drip with ovalbumin (OVA) were performed. Saline was used instead of OVA for negative control. Probiotic preparations of LFK and TN were orally administrated for 42 days [60 mg (0.5 ml)/d] in LFK-fed and TN-fed mice, respectively. The positive and negative control mice received saline orally for 42 days. Nasal rubbing and sneezing were monitored on d 21, d 27, and d 35. After the final challenge, mice were sacrificed on d 42, and eosinophilic infiltration into the nasal mucosa was quantified (H&E stain). IFN-gamma, IL4 and OVA-specific IgE levels in the sera and splenocyte culture supernatants were determined by ELISA kits.. Nasal rubbing of LFK-fed mice was significantly reduced compared to the positive control group on day 27 (t = 2.95, P = 0.028). Both in the LFK-fed and TN-fed mice, nasal rubbing (t value was 3.75 and 3.06, P value was 0.005 and 0.011, respectively) and sneezing (t value was 2.56 and 3.35, P value was 0.038 and 0. 01, respectively) were significantly decreased compared to the positive control group on d 35. The H&E strain section of nasal tissue showed that eosinophil influx into the nasal mucosa decreased significantly both in the LFK-fed and TN-fed mice compared to the positive control group on day 42 (t value was 3.44 and 2.97, P value was 0.014 and 0.025, respectively); however, the LFK-fed mice and TN-fed mice had significant eosinophil influx into the nasal mucosa than that in the negative control group (t value was 2.54 and 3.39, P value was 0.044 and 0.015, respectively). There were no significant differences in the serum levels of IL-4 and OVA-specific IgE, as well as the levels of IFN-gamma and IL-4 in splenocyte culture supernatants between the LFK-fed group and positive control group on d 42 (all P > 0.05). Interestingly, the TN-fed mice had significantly higher serum levels of IFN-gamma compared to the LFK-fed mice [TN-fed mice: (27.07 +/- 3.83) pg/ml, LFK-fed mice: (14.83 +/- 0.99) pg/ml; Z = 2.49, P = 0.016], but not the negative control group [negative control group: (37.12 +/- 1.65) pg/ml; Z = 1.18, P = 0.343] on day 42. The serum levels of IL-4 were significantly lower in the TN-fed mice than those in the positive control group [TN-fed mice: (34.48 +/- 7.53) pg/ml, positive control group: (58.68 +/- 6.59) pg/ml; Z = 2.11, P = 0.035]; however, the levels were significantly higher in the TN-fed mice than those in the negative control group [negative control group: (20.22 +/- 1.75) pg/ml; Z = 2. 31, P = 0.021]. The TN-fed mice had significantly higher levels of IFN-gamma in splenocyte culture supernatants compared to the LFK-fed mice (Z = 2.72, P = 0.03) and the positive control group (Z = 2.30, P = 0.029), whilst the splenocyte culture supernatant levels of IL-4 (Z = 2.12, P = 0.034) and the serum levels of OVA-specific IgE (Z = 2.31, P = 0.021) were significantly lower in the TN-fed mice compared to the positive control mice.. It is suggested that oral administration of probiotic LFK or TN may alleviate nasal symptoms and reduce nasal eosinophilia in the murine AR model. TN supplementation has obviously regulatory effects on the cytokine levels of IFN-gamma and IL-4, and significantly inhibitory effects on antigen-specific IgE levels.

Topics: Administration, Oral; Animals; Anti-Allergic Agents; Cytokines; Disease Models, Animal; Enterococcus; Eosinophilia; Eosinophils; Interleukin-4; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Probiotics; Rhinitis, Allergic

Sphingosine-1-phosphate (S1P) plays a crucial role in homeostasis of the immune system by regulating lymphocyte recirculation and inflammatory cell recruitment. The levels of S1P are tightly controlled through regulated production and controlled breakdown by sphingosine-lyase (SL). The S1P analogue FTY720 has been developed as an immunosuppressant in transplantation and tested as a treatment for various inflammatory diseases. FTY720 exploits S1P biology by acting as a S1P1 and S1P 3 agonist and by inhibiting S1P breakdown by SL.. Here, we investigate interfering S1P in allergic rhinitis (AR) and its way of action.. Allergic rhinitis was induced by sensitizing mice to ovalbumin (OVA) and challenging the nose with OVA allergen. At the time of allergen challenge, mice received topical intranasal treatment with FTY720. To address the relative contribution of SL inhibition in mediating its effects, some mice were treated with the SL inhibitor 2-acetyl-4-tetrahydroxybutyl (THI).. FTY720 treatment resulted in significantly fewer eosinophils, mast cells and dendritic cells in the nasal mucosa of AR animals, compared with diluent treatment. Levels of IL-4, IL-5, IL-10 and IL-13 produced by lymph node cells fell significantly in FTY720-treated animals. Moreover, FTY720 proved potent enough to suppress inflammation in a model of persistent AR. In vitro and in vivo experiments indicate that FTY720 impaired Th2 differentiation and proliferation important in driving eosinophilia and induced apoptosis in mast cells.. Our results indicate that interfering with S1P metabolism is a powerful and feasible strategy to develop new topical agents that suppress AR.

Topics: Administration, Topical; Animals; Apoptosis; Disease Models, Animal; Drug Delivery Systems; Eosinophils; Fingolimod Hydrochloride; Immunosuppressive Agents; Lysophospholipids; Mast Cells; Mice; Mice, Inbred Strains; Ovalbumin; Propylene Glycols; Random Allocation; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Sensitivity and Specificity; Sphingosine; Th2 Cells

T(H)17 responses have recently been implicated to play a role in allergic airway diseases, but their local expression in the setting of allergic rhinitis (AR) and their regulation in allergic airway diseases remain unclear.. We sought to investigate the regulatory role of Clara cell 10-kDa protein (CC10), an endogenous regulator of airway inflammation, on T(H)17 responses in the setting of AR.. Wild-type and homozygous CC10-null mice were used to establish an ovalbumin (OVA)-induced AR model. Human recombinant CC10 was given during sensitization or challenge. T(H)17 responses in human subjects and mice were examined by using flow cytometry, quantitative RT-PCR assay, immunohistochemistry, and ELISA. The direct effect of CC10 on T(H)17 cells and CD11c(+) dendritic cells (DCs) was studied by means of cell culture. Adoptive transfer was used to examine the influence of CC10-conditioned DCs on airway inflammation. The regulatory effect of CC10 on the expression of the CCL20 gene was tested by using the BEAS-2B cell line.. Compared with those of control subjects, T(H)17 responses were enhanced in the nasal mucosa of patients with AR. CC10-null mice with AR showed enhanced T(H)17 responses, and CC10 treatment significantly decreased T(H)17 responses. CC10 had no direct effect on in vitro T(H)17 cell differentiation. CC10 could significantly decrease the expression of OX40 ligand, IL-23, and IL-6 but enhance CD86 and TGF-β expression in DCs. Importantly, CC10 was able to inhibit T(H)17 cell polarization in the presence of OVA-pulsed DCs. CC10 pretreatment inhibited T(H)17 responses elicited by adoptive transfer of OVA-pulsed DCs. Furthermore, CC10 decreased the expression of CCL20 in BEAS-2B cells induced by inflammatory cytokines.. T(H)17 responses are enhanced in patients with AR, and CC10 inhibits T(H)17 responses through modulation of the function of DCs.

Topics: Adoptive Transfer; Animals; B7-2 Antigen; Case-Control Studies; Cell Differentiation; Cell Line; Chemokine CCL20; Dendritic Cells; Eosinophils; Epithelial Cells; Humans; Interleukin-23; Interleukin-6; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nasal Mucosa; Neutrophils; Ovalbumin; OX40 Ligand; Pneumonia; Receptors, Formyl Peptide; Recombinant Proteins; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Th17 Cells; Transforming Growth Factor beta; Uteroglobin

The pathophysiologic mechanism of allergy is dependent on the action of many redox-sensitive proinflammatory mediators. However, even though redox disturbances are believed to be a hallmark of inflammation, little is known of the effect of redox imbalance to the pathophysiology of allergic rhinitis. We thus opted to investigate the relation of oxidative stress and allergic rhinitis, through the utilization of a potent antioxidant substance (N-acetylcysteine [NAC]) in a rat model of allergic rhinitis and the evaluation of its action on specific markers of inflammation.. NAC (50 mg/kg and 250 mg/kg) was intraperitoneally administered to ovalbumin (OVA)-sensitized rats prior to intranasal challenge with OVA. Mucosal congregation of inflammatory cells (eosinophils and mast cells), mucosal expression of redox-sensitive enzymes (inducible nitric oxide synthase [iNOS] and cyclooxygenase 2 [COX-2]), and the blood levels of a key proinflammatory mediator (tumor necrosis factor-α [TNF-α]) were evaluated.. Intranasal OVA challenges lead to mucosal inflammation, induction of the mucosal expression of iNOS and COX-2 and elevation of TNF-α blood levels. NAC significantly inhibited accumulation of inflammatory cells and downregulated iNOS expression and TNF-α serum levels. The role of COX-2 appeared to be 2-fold and its expression was divergently modulated by NAC.. Our findings suggest that redox balance is involved in the pathophysiology of allergic rhinitis in rats and that NAC can potentially suppress the allergen-induced nasal inflammatory cascade. The investigation of the role of oxidative stress in atopy could help in the evaluation of the therapeutic potential of antioxidant substances in allergic diseases.

Topics: Acetylcysteine; Administration, Intranasal; Allergens; Animals; Anti-Inflammatory Agents; Antioxidants; Cyclooxygenase 2; Disease Models, Animal; Male; Nasal Mucosa; Nitric Oxide Synthase Type II; Ovalbumin; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Tumor Necrosis Factor-alpha

Although CD23-dependent transcytosis of IgE and IgE-derived immune complexes across respiratory epithelial cells is likely to play a pivotal role in the initiation and development of airway allergic inflammation, there is currently a lack of physiological support for this phenomena to suggest that the targeting of CD23 could be used as a means of therapeutic intervention. The present study was designed to detect the CD23 expression in the nasal mucosa of allergic rhinitis (AR) murine model by immunohistochemistry and western blotting, and to investigate whether intranasal anti-CD23 treatment could inhibit allergen-induced upper airway inflammation in the AR model. This is the first report to show that CD23 was constitutively expressed in murine nasal epithelial cells, and its expression was significantly up-regulated in the AR murine model. In vivo, the up-regulation of CD23 expression was correlated with increased serum IL-4 levels. Following intranasal anti-CD23 treatment, nasal symptoms were alleviated and histopathologic examination showed a significant decrease in eosinophilic infiltration. Meanwhile, ELISA analysis showed levels of serum leukotriene C4 (LTC4), eosinophil cation protein (ECP), ovalbumin (OVA)-specific IgE and IL-4 also significantly decreased, as were LTC4 and OVA-specific IgE in the nasal lavage fluid. Furthermore, Western blotting analysis showed that ECP expression in the nasal mucosa was down-regulated. Finally, flow cytometric analysis revealed anti-CD23 treatment inhibited Th2 cell responses. These results indicate that intranasal anti-CD23 treatment can reduce allergic responses in a murine model of allergic rhinitis.

Topics: Administration, Intranasal; Allergens; Animals; Budesonide; Disease Models, Animal; Down-Regulation; Eosinophil Cationic Protein; Eosinophils; Epithelial Cells; Female; Hypersensitivity; Immunoglobulin E; Inflammation; Interleukin-4; Leukotriene C4; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Random Allocation; Receptors, IgE; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Th2 Cells; Up-Regulation

The association of allergic diseases and disease activity in systemic lupus erythematosus (SLE, lupus) is controversial. The study investigates lupus activity-related differences in the induction of late allergic rhinitis (LAR) in the female NZB×NZW(B/W)F(1) mouse model for lupus. The LAR, which is induced by ovalbumin, was examined during the preactive (before clinical onset) and active (after clinical onset) phases in mice. Induction of LAR was less severe in mice with active lupus in contrast to clinically healthy lupus mice that developed a more severe allergic rhinitis. Inhibition of the development of LAR may be due to reduced eosinophilia and local interleukin-4 secretion during active autoimmune disease. In addition, systemic interferon-γ, but not IL-4, production increased during the active phase, but not the preactive phase. This suggests that the predominating Th1 lineage commitment in mice with active lupus may be responsible for the inhibition of the allergic Th2 response. The present study may shed some light on the controversy of the prevalence of allergic diseases in SLE patients.

Topics: Animals; Antibodies, Antinuclear; Blood Urea Nitrogen; Creatinine; Eosinophilia; Eosinophils; Female; Inflammation; Interferon-gamma; Interleukin-4; Leukocytes; Lupus Erythematosus, Systemic; Lymphocyte Count; Mice; Mice, Inbred BALB C; Mice, Inbred NZB; Nasal Lavage Fluid; Neutrophils; Ovalbumin; Proteinuria; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Spleen; Th1 Cells; Th2 Cells

Bamboo salt (BS) is a specially processed salt according to the traditional recipe using sun-dried salt (SDS) and bamboo in Korea. The present study investigated the effects and mechanism of BS, SDS, NaCl, or mineral mixture (containing zinc, magnesium, and potassium) on ovalbumin (OVA)-induced allergic rhinitis (AR) animal model. The increased number of rubs was inhibited by the oral administration of BS, SDS, NaCl, mineral mixture, or nose inhalation of BS. The increased levels of IgE, histamine, and interleukin (IL)-1β in serum were reduced by BS. The level of interferon-γ was increased, whereas the level of IL-4 was reduced on the spleen tissue of BS-treated mice. In the BS-treated mice, the number of eosinophils and mast cells infiltration increased by OVA-sensitization were also decreased. Protein levels of inflammatory cytokines were reduced by BS or NaCl administration in the nasal mucosa of the AR mice. In addition, BS inhibited caspase-1 activity in the nasal mucosa tissue. In activated human mast cells, BS significantly inhibited the production of IL-1β and thymic stromal lymphopoietin and activation of caspase-1. Our data indicate that BS has anti-allergic and anti-inflammatory effects by regulating of caspase-1 activation in AR mice and in vitro models.

Topics: Animals; Bambusa; Caspase 1; Cell Line; Cytokines; Food Handling; Histamine; Humans; Immunoglobulin E; Mast Cells; Mice; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Sodium Chloride, Dietary

To elucidate the functions of nuclear factor kappa B (NF-κB) in mucin hypersecretion in allergic rhinitis (AR), we examined the in vivo effects of an NF-κB inhibitor, ammonium pyrrolidine dithiocarbamate (PDTC), on mucin 5 subtype AC (MUC5AC) expression in the nasal mucosa of ovalbumin-sensitized rats.. Randomized animal study.. Academic medical center.. Sprague Dawley rats were randomized into a control group (group A), an AR model group (group B), and an AR model treated with an NF-κB inhibitor (group C). Rats in groups B and C were sensitized systemically and locally by ovalbumin injection and inhalation, whereas group A was treated with normal saline in place of ovalbumin. Pyrrolidine dithiocarbamate (100 mg/kg/d) was given to group C by intraperitoneal injection for 5 days. NF-κBp65, MUC5AC, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were detected by immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay, or real-time polymerase chain reaction.. NF-κB was activated in group B, and significant NF-κBp65 protein was expressed in the nucleus of cells from the nasal mucosa, resulting in upregulated transcription from TNF-α and IL-6 genes, as well as increased contents of TNF-α and IL-6 in the nasal lavage fluids. Pyrrolidine dithiocarbamate inhibited nuclear localization of NF-κBp65 and subsequent downregulation of the transcription and secretion of TNF-α and IL-6. MUC5AC was upregulated in group B but reduced in a time-dependent manner after inhibition of NF-κB activation.. NF-κB activation might induce MUC5AC hypersecretion in AR rats by inflammatory cytokines TNF-α and IL-6.

Topics: Animals; Interleukin-6; Mucin 5AC; Nasal Mucosa; NF-kappa B; Ovalbumin; Pyrrolidines; Random Allocation; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Thiocarbamates; Transcription Factor RelA; Tumor Necrosis Factor-alpha; Up-Regulation

The purpose of the present study was to investigate the effect of nucleotide-binding oligomerization domain 1 (NOD1), an innate immune sensor, on allergic inflammation and induction of regulatory T cells in a mouse model of allergic rhinitis. We also aimed to explore whether there were differences in the effect of NOD1 ligand according to the timing of administration. Study Design An in vivo study using an animal model.. Catholic Research Institutes of Medical Science.. Forty BALB/c mice were divided into 4 groups: control, OVA, pre-NOD1, and post-NOD1. Ovalbumin (OVA) was used for sensitization and challenge. The pre-NOD1 group received NOD1 ligand intranasally before sensitization, whereas the post-NOD1 group received it after sensitization. The effects of allergic inflammation and regulatory T cells were compared among the groups.. In the post-NOD1 group, serum OVA-specific IgE, eosinophil counts, interleukin (IL)-13 levels, and GATA-3 mRNA expression were significantly increased and Foxp3(+) mRNA expression and CD4(+) Foxp3(+) T cells were decreased compared with the OVA group. In the pre-NOD1 group, Foxp3 mRNA expression and CD4(+) Foxp3(+) T cells were significantly decreased compared with the OVA group. Although not significant, the pre-NOD1 group showed increases in serum OVA-specific IgE, eosinophil counts, IL-13 levels, and GATA-3 mRNA expression compared with the OVA group.. The innate immune response through NOD1 enhances allergen-specific Th2 response and suppresses induction of regulatory T cells in a mouse model of allergic rhinitis, and the effects are different depending on the timing of exposure to NOD1 ligand.

Topics: Animals; CD4-Positive T-Lymphocytes; Eosinophils; Female; Forkhead Transcription Factors; GATA3 Transcription Factor; Immunity, Innate; Immunoglobulin E; Interleukin-13; Ligands; Mice; Mice, Inbred BALB C; Nod1 Signaling Adaptor Protein; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; RNA, Messenger; T-Lymphocytes, Regulatory

Hypoxia-inducible factor 1α (HIF-1α) is an important regulator of immune and inflammatory responses. We hypothesized that nasal allergic inflammation is attenuated by HIF-1α inhibition and strengthened by HIF-1α stabilization.. To elucidate the role of HIF-1α in a murine model of allergic rhinitis (AR).. Mice were pretreated with the HIF-1α inhibitor 2-methoxyestradiol (2ME2) or the HIF-1α inducer cobalt chloride (CoCl(2)) in an established AR murine model using ovalbumin (OVA)-sensitized BALB/c mice. HIF-1α and vascular endothelial growth factor (VEGF) expression in nasal mucosa was measured and multiple parameters of allergic responses were evaluated.. HIF-1α and VEGF levels were locally up-regulated in nasal mucosa during AR. Inflammatory responses to OVA challenge, including nasal symptoms, inflammatory cell infiltration, eosinophil recruitment, up-regulation of T-helper type 2 cytokines in nasal lavage fluid, and serum OVA-specific IgE levels were present in the OVA-challenged mice. 2ME2 effectively inhibited HIF-1α and VEGF expression and attenuated the inflammatory responses. Stabilization of HIF-1α by CoCl(2) facilitated nasal allergic inflammation. HIF-1α protein levels in nasal airways correlated with the severity of AR in mice.. HIF-1α is intimately involved in the pathogenesis of nasal allergies, and the inhibition of HIF-1α may be useful as a novel therapeutic approach for AR.

Topics: 2-Methoxyestradiol; Animals; Cobalt; Cytokines; Estradiol; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoglobulin E; Immunohistochemistry; Inflammation; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Signal Transduction; Vascular Endothelial Growth Factor A

To study the immunoregulatory effect of an optimal Chinese herbal monomer compound, which consists of three monomers, namely, icariin, baicalin and Astragalus saponin I, in a mouse model of allergic rhinitis.. A mouse model of allergic rhinitis was established by intraperitoneal injection of ovalbumin and aluminum hydroxide gel suspension. The splenic lymphocytes of the mice were separated, cultured in 96-well plates and divided into three groups: control group, concanavalin A group and compound group. Splenic lymphocyte proliferation was detected by cell counting kit-8 method at different time points. Cell cycle distribution was observed by flow cytometry (FCM) also at different time points. The changes of intracellular calcium concentration of splenic lymphocytes were measured by fluorescence microplate reader after the cells were incubated with fluorescence probe Fluo-3/AM.. The Chinese herbal monomer compound could inhibit cell proliferation induced by concanavalin A (P<0.01). And the inhibition presented a time-effect relationship. With extending of the action time, the inhibition rate gradually increased and reached peak at the 48th hour. FCM test revealed the fact that concanavalin A could promote cells to enter into the mitosis by reducing the percentage of cells in G0/G1 phases while increasing the percentage of cells in S and G(2)/M phases. Compared with the concanavalin A, the compound could increase the percentage of cells in G(0)/G(1) phases and at the same time reduce the percentage of cells in S and G(2)/M phases at different time points, with the effect most significant at the 24th hour (P<0.05 or P<0.01). The results of the test taken by the fluorescence microplate reader revealed that the fluorescence value of the concanavalin A group increased with time in the previous 24 h while the compound could reduce this trend obviously, thus reduce the intracellular calcium concentration (P<0.01).. The Chinese herbal monomer compound can inhibit the proliferation of cultured splenic lymphocytes of mice with allergic rhinitis. The effects of the compound of lowering intracellular calcium concentration and arresting cell cycle at G(0)/G(1) phases from entering into S and G(2)/M phases are responsible for its antiproliferation activity.

Topics: Animals; Cell Proliferation; Cells, Cultured; Drug Compounding; Drugs, Chinese Herbal; Flavonoids; Immunomodulation; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Saponins; Spleen; Triterpenes