leukotriene-c4 and Rhinitis--Allergic

Current medications to treat allergic rhinitis (AR) include antihistamines, corticosteroids, and anti-leukotrienes. In the present study, we investigated the effects of combination therapy; using these drugs, and evaluates the AR-related markers and parameters in an animal model. After inducing BALB/c mice AR models, the animals were treated with either pranlukast, loratadine, fluticasone, loratadine + fluticasone, loratadine + pranlukast, fluticasone + pranlukast, or loratadine + fluticasone + pranlukast. Clinical symptoms, Immunoglobulin (Ig)G1, ovalbumin (OVA)-specific and total IgE, leukotriene (LT)B4, LTC4, histamine, thymic stromal lymphopoietin (TSLP) serum levels, and interleukin 4 level in the nasal lavage fluid were determined. The expressions of HRH1, CysLT1R, NLR3, Caspase-1, and MUC5a were studied. Allergic symptoms (nasal rubbing and sneezing), serum Igs (IgG1, total and OVA-specific IgE), eicosanoids (LTB4 and LTC4), histamine, TSLP, and IL-4 as well as gene expressions of MUC5a, Caspase-1, NLR3, HRH1, and CysLT1R were reduced in the animals receiving each of the therapeutic regimens; however, more pronounced effects were seen in the group treated with the triple combined protocol (loratadine + fluticasone + pranlukast). The combination of the loratadine, fluticasone, and pranlukast can effectively control the symptoms of AR probably via modulating several related mechanisms at early and late phases of allergic responses.

Topics: Allergens; Animals; Caspase 1; Fluticasone; Histamine; Immunoglobulin E; Leukotriene C4; Loratadine; Mice; Rhinitis, Allergic

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

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

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

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