transforming-growth-factor-beta and Rhinitis--Allergic

Topics: Animals; Asthma; Chronic Disease; Humans; Multigene Family; Rhinitis, Allergic; Signal Transduction; Sinusitis; Transforming Growth Factor beta

Timely and successful resolution of acute inflammation plays a crucial role in preventing the development of chronic airway inflammation in allergic rhinitis (AR). This study intends to assess the serum levels of pro-inflammatory leukotriene B4 (LTB4), anti-inflammatory mediators, including resolvin E1 (RvE1), RvD1, IL-10, and TGF-β, besides mRNA expression level of G-protein coupled receptor 120 (GPR120) and peroxisome proliferator-activated receptor-γ (PPAR-γ) receptors in peripheral blood leukocytes of AR patients. Thirty-seven AR patients and thirty age- and gender-matched healthy subjects were enrolled in this study. The serum levels of LTB4, RvE1, RvD1, IL-10, and TGF-β were measured using enzyme-linked immunosorbent assay (ELISA) technique, and the mRNA expression level of GPR120 and PPAR-γ was assessed by the real-time PCR method. The serum levels of RvE1 and LTB4 were significantly higher in patients with AR than in healthy subjects (P < 0.01 and P < 0.0001, respectively). However, a significantly lower ratio of RvE1 and RvD1 to LTB4 was found in patients with AR relative to healthy subjects (P < 0.05 and P < 0.0001, respectively). Likewise, the serum levels of both IL-10 and TGF-β cytokines were significantly reduced in patients with AR compared to healthy subjects (P < 0.01 and P < 0.0001, respectively). Furthermore, the mRNA expression of PPAR-γ was significantly lower in patients with AR than in healthy subjects (P < 0.05). Our findings indicate that imbalanced pro-resolving lipid mediator RvE1 and pro-inflammatory LTB4 might contribute to the defective airway inflammation-resolution and subsequent progression toward chronic inflammation in AR patients.

Topics: Adult; Eicosapentaenoic Acid; Female; Humans; Interleukin-10; Leukotriene B4; Male; PPAR gamma; Receptors, G-Protein-Coupled; Rhinitis, Allergic; Transforming Growth Factor beta

Topics: Animals; Antigens, Dermatophagoides; Child; Dermatophagoides farinae; Humans; Interleukin-13; Leukocytes, Mononuclear; Rhinitis, Allergic; RNA, Messenger; Sublingual Immunotherapy; Transforming Growth Factor beta; Treatment Outcome

MicroRNA (miR)-146a, as an important immune regulatory factor with an anti-inflammatory effect, plays a crucial role in regulatory T-cell (Tregs) differentiation and function in allergic rhinitis (AR). The present study aimed to investigate the regulatory mechanism employed by miR-146a to control Treg differentiation and function in AR.. Expression of miR-146a and STAT5b in peripheral blood mononuclear cells (PBMCs) and nasal mucosa from patients with AR was detected by qPCR and Western blotting. Tregs were quantified by flow cytometry in miR-146a knockdown or STAT5b knockdown PBMCs. FOXP3, IL-10, and TGF-β levels were detected by Western blotting or ELISA in miR-146a knockdown or STAT5b overexpressing PBMCs, as well as in STAT5b knockdown PBMCs overexpressing miR-146a. The effect of miR-146a on STAT5b was observed by luciferase assay and knockdown experiments.. Levels of miR146a and STAT5b in the nasal mucosa or PBMCs were significantly lower in the AR group than in the control group. There were significantly fewer Tregs in miR-146a knockdown or STAT5b knockdown PBMCs compared to control PBMCs. Expression of FOXP3, IL-10, and TGF-β was decreased in the miR-146a knockdown group but increased in the STAT5b overexpression group. In contrast, miR-146a overexpression increased the levels of these factors, but knockdown of STAT5b significantly inhibited this effect. Luciferase assay and knockdown experiments showed that miR-146a bound directly to STAT5b.. miR-146a enhances Treg differentiation and function in AR by positively targeting STAT5b.

Topics: Cell Differentiation; Forkhead Transcription Factors; Humans; Interleukin-10; Leukocytes, Mononuclear; MicroRNAs; Rhinitis, Allergic; STAT5 Transcription Factor; T-Lymphocytes, Regulatory; Transforming Growth Factor beta

Topics: Animals; Apoptosis; Biomarkers; Cytokines; Disease Models, Animal; Glucosides; Immunoglobulin E; Immunohistochemistry; Male; Mice; Oxidative Stress; Paeonia; Plant Extracts; Rhinitis, Allergic; Signal Transduction; Smad7 Protein; Transforming Growth Factor beta

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

Allergic rhinitis is a growing problem worldwide. Currently the only treatment that can modify the disease is antigen-specific immunotherapy, but its mechanism of action is not fully understood.. We comprehensively investigated the role and changes of antigen-specific T cells before and after sublingual immunotherapy (SLIT) for Japanese cedar pollinosis.. We cultured peripheral blood mononuclear cells obtained both before and 1 year after initiating SLIT and used a combination of single-cell RNA sequencing and repertoire sequencing. To investigate biomarkers, we used cells from patients participating a phase 2/3 trial of SLIT tablets for Japanese cedar pollinosis and cells from outpatients with good and poor response.. Antigen-stimulated culturing after SLIT led to clonal expansion of T. The combination of single-cell RNA sequencing and repertoire analysis helped reveal part of the underlying mechanism: SLIT promotes the expression of MSC on pathogenic T

Topics: Allergens; Biomarkers; Cryptomeria; Humans; Immunologic Factors; Interleukin-2; Leukocytes, Mononuclear; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Sublingual Immunotherapy; Transforming Growth Factor beta

The profile of inflammatory and suppressing cytokines is important to contribute to the disruption of TH1/TH2 balance in Allergic rhinitis (AR).. This study aimed to assess the expression levels of IL-6, IL-18, IL-21, IL-23, and TGF-β in nasal biopsies in AR patients and evaluate its correlation with the severity of AR.. The study included 30 patients with mild persistent allergic rhinitis (MPAR), patients with moderate-to-severe (M/S) PAR, and 30 healthy individuals. The biopsies of nasal inferior turbinate mucosa were collected from each participant. The expression of IL-6, IL-18, IL-21, IL-23, and TGF-β was evaluated by the quantitative real-time polymerase chain reaction. The degree of eosinophil infiltration into the nasal mucosa, blood eosinophils, and total serum IgE level were also measured.. The expression of IL-6, IL-18, and IL-23 in patients with AR significantly increased compared to the control group. Conversely, the gene expression of the TGF-β declined in the M/S PAR group rather than the AR- group. The data did not show a significant difference in the expression of the IL-21 gene between AR+ and AR- groups.. We suggested that inflammatory cytokines including IL-6, IL-18, and IL-23 may be involved in the severity of AR and associated with markers of inflammation.

Topics: Cytokines; Humans; Interleukin-18; Interleukin-23; Interleukin-6; Interleukins; Nasal Mucosa; Rhinitis, Allergic; RNA, Messenger; Transforming Growth Factor beta

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

CD8. Prospective cross-sectional study.. Patients with AR were enrolled. PBMCs were obtained, and CD4. The percentages of CD4. The findings demonstrate that CD8. 3 Laryngoscope, 131:E316-E323, 2021.

Topics: Adult; Case-Control Studies; CD8-Positive T-Lymphocytes; Cells, Cultured; Female; Healthy Volunteers; Humans; Interleukin-10; Interleukin-4; Interleukin-5; Male; Middle Aged; Primary Cell Culture; Rhinitis, Allergic; T-Lymphocytes, Regulatory; Transforming Growth Factor beta

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

The polymorphisms inside microRNA target sites locating in the 3'-UTR region may introduce the micro-RNA-binding changes, which may regulate the gene expression and correlate with the potential diseases.. We aimed to investigate whether the polymorphisms in microRNA target sites of transforming growth factor beta (TGF-β) signaling pathway genes are associated with the susceptibility of mite-sensitized allergic rhinitis (AR) in a Han Chinese population.. In this case-control study, 454 AR patients and 448 healthy controls were recruited. Three HapMap single-nucleotide polymorphisms (SNPs) were mapped to putative microRNA recognition sites and genotyped by TaqMan allelic discrimination assay.. The genotype and allele frequencies of 3 SNPs (rs1590 in TGFBR1; rs1434536 and rs17023107 in BMPR1B) showed lack of significant association with AR. However, in the subgroup analysis, the TG, GG, and TG/GG genotypes of rs1590 exhibited significantly increased risk of AR in the male subgroup (TG: adjusted OR = 1.57, 95% CI = 1.08-2.31; GG: adjusted OR = 1.76, 95% CI = 1.09-2.86; TG/GG: adjusted OR = 1.62, 95% CI = 1.13-2.33). The CT genotypes of rs17023107 might have potential to protect against AR in the patients age of <15 years (adjusted OR = 0.37, 95% CI = 0.14-0.95) and the males (adjusted OR = 0.48, 95% CI = 0.25-0.95). No significant association was found between SNPs and the total serum IgE level.. In a Han Chinese population, stratified by age and gender, susceptibility to mite-sensitized AR may be associated with 2 SNPs (rs1590 and rs17023107) in microRNA target sites of TGF-β signaling pathway genes.

Topics: 3' Untranslated Regions; Adolescent; Adult; Alleles; Biomarkers; Child; Disease Susceptibility; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Immunoglobulin E; Male; MicroRNAs; Polymorphism, Single Nucleotide; Rhinitis, Allergic; Signal Transduction; Transforming Growth Factor beta; Young Adult

This study was designed to investigate the potential effects and underlying mechanism of adipose tissue-derived mesenchymal stem cells (MSCs) on allergic inflammation compared to Montelukast as an antileukotriene drug in a rat model of allergic rhinitis (AR). The effect of MSCs was evaluated in albino rats that were randomly divided into four (control, AR, AR + Montelukast, and AR + MSCs) groups. Rats of AR group were sensitized by ovalbumin (OVA) and then challenged with daily nasal drops of OVA diluted in sterile physiological saline (50 μL/nostril, 100 mg/mL, 10% OVA) from day 15 to day 21 of treatment with/without Montelukast (1 h before each challenge) or MSCs I/P injection (1 × 10⁶ MCSs; weekly for three constitutive weeks). Both Montelukast and MSCs treatment started from day 15 of the experiment. At the end of the 5th week, blood samples were collected from all rats for immunological assays, histological, and molecular biology examinations. Both oral Montelukast and intraperitoneal injection of MSCs significantly reduced allergic symptoms and OVA-specific immunoglobulin E (IgE), IgG1, IgG2a and histamine as well as increasing prostaglandin E2 (PGE2). Further analysis revealed that induction of nasal innate cytokines, such as interleukin (IL)-4 and TNF-α; and chemokines, such as CCL11 and vascular cell adhesion molecule-1 (VCAM-1), were suppressed; and transforming growth factor-β (TGF-β) was up-regulated in Montelukast and MSCs-treated groups with superior effect to MSCs, which explained their underlying mechanism. In addition, the adipose tissue-derived MSCs-treated group had more restoring effects on nasal mucosa structure demonstrated by electron microscopical examination.

Topics: Adipose Tissue; Animals; Cells, Cultured; Chemokine CCL11; Disease Models, Animal; Interleukin-4; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Nasal Mucosa; Rats; Rhinitis, Allergic; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

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

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

This study aims to explore the role of the Th17 to Treg cell ratio in children with OSA and its relationship with allergic rhinitis.. The study included 127 children diagnosed with OSA by polysomnography (PSG) testing and 29 children without OSA. The 127 children with OSA were divided into the following groups: OSA with moderate adenoidal hypertrophy (n=47), OSA with severe adenoidal hypertrophy (n=49), and OSA complicated by allergic rhinitis (AR) (n=31). The adenoids of the 29 children without OSA were mildly hypertrophic. We measured the number of Th17 and Treg cells, the levels of related serum cytokines in cellular secretions, and the expression of key transcription factors in both the peripheral blood and adenoid tissue. The Th17/Treg ratio was calculated and analyzed between groups. The numbers of Th17 and Treg cells were measured by flow cytometry; the secreted IL-17, IL-10, and TGF-β were measured by ELISA; and the expression levels of RORγt and Foxp3 were measured by RT-PCR.. Compared with the control group, OSA children exhibited a significant increase in the number of peripheral Th17 cells, Th17-related cytokine secretion (IL-17), and RORγt mRNA levels, whereas they exhibited a decrease in the number of Treg cells, Treg-related cytokine secretions (IL-10, TGF-β) and Foxp3 mRNA levels. The Th17/Treg ratio was higher (p<0.05) in the OSA groups than in the control group. The Th17/Treg ratio was correlated with the size of the adenoids. We also found that the Th17/Treg balance in OSA patients was complicated by allergic rhinitis; the increase was significantly larger in the AR group (p<0.05, p=0.021) than in OSA groups without AR. These results were observed in both the peripheral blood and local adenoid tissue.. The Th17/Treg imbalance may increase the risk of developing OSA, and AR may promote the development of the disease. These results provide an alternative explanation for OSA pathogenesis that warrants additional research and presents new directions for the prevention and treatment of OSA in children.

Topics: Adenoids; Child; Child, Preschool; Female; Flow Cytometry; Forkhead Transcription Factors; Humans; Hypertrophy; Interleukin-10; Interleukin-17; Lymphocyte Count; Male; Nuclear Receptor Subfamily 1, Group F, Member 3; Organ Size; Rhinitis, Allergic; RNA, Messenger; Sleep Apnea, Obstructive; T-Lymphocytes, Regulatory; Th17 Cells; Transforming Growth Factor beta

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