Objective: To exploit the role of TRPV1 using TRPV1 antagonist such as N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine -1(2H)-carboxamide (BCTC) and TRPV1 knockout mice in allergic rhinitis mice models and using samples of patients with allergic rhinitis and to evaluate the molecular mechanism of TRPV1 in CD4+ T cell mediated signaling pathway in allergic rhinitis.
Methods: TRPV1 expression was measured in CD4+ T cell and cytokine analysis and T cell receptor signaling pathways were evaluated in BCTC pretreated T cell lines and TRPV1 (-/-) T cells. Allergic parameters were evaluated using TRPV1 antagonists and TRPV1 knockout mice in OVA-challenged mice model. Additionally, TRPV1 expressions were assessed in patients with allergic rhinitis.
Results: TRPV1 expression was localized in CD4+ T cell. BCTC pretreatment and TRPV1 knockout suppressed T cell cytokine production and suppressed T cell receptor signaling pathways, including NF-kB, MAP kinase and NFAT signaling in both Jurkat cell line and CD4 + T cells in vitro. TRPV1 antagonists (BCTC and theobromine) significantly reduced allergic parameters such as symptoms, total- and ova-specific IgE levels in the mice model of allergic rhinitis. In TRPV1 knockout and BCTC treated mice, nasal eosinophil infiltration and nasal mucosal cytokines transcriptional activities were decreased, when compared OVA-challenged wild-type mice. In human nasal mucosa, TRPV1+ inflammatory cells was frequently observed. TRPV1/CD4 double positive inflammaotry cells were increased in nasal mucosa in patients with allergic rhinitis as compared with non-allergic rhinitis and normal controls.
Conclusion: TRPV1 activation on CD4+ T cells is involved in TCR signaling and could be a novel therapeutic strategy in allergic rhinitis.