| Summary: | 碩士 === 國立成功大學 === 微生物及免疫學研究所 === 102 === Allergic rhinitis (AR) is a disease with symptom of nasal airway hyperresponsiveness and mucosal inflammation mediated by IgE-associated processes. Nerve growth factor (NGF), a neurotrophin, has been shown to play an important role in neuroimmune responses by augmenting an existing type 2 T helper cell (TH2) immune response. Since chitin exhibits anti-inflammatory properties by inhibiting the development of allergic TH2 response, we aimed to assess the effect of the soluble derivatives of chitin—water soluble chitosan (WSC) on the NGF in a mouse model of Dermatophagoides pteronyssinus (Der p)-induced AR. First, we established an NGF-mediated AR toward augmenting systemic total and Der p-specific IgE levels, upper airway hyperresponsiveness, and local TH2 related immune response including the infiltration of eosinophils and degranulation of mast cells as well as TH2 related cytokines production in the nasal septum and nasal cavity lavage fluids. Interestingly, intranasal administration of WSC reduced allergic inflammation and improved the upper airway hyperresponsiveness. The expression of NGF and its related low affinity p75 neurotrophin receptors (p75NTR) as well as high affinity tyrosine kinase receptor A (TrkA) recptors in nasal epithelium of Der p-stimulated mice also repressed. Next, we used human nasal septum epithelial cell line (RPMI-2650) to investigate the detail mechanisms of candidate anti-allergic agents—WSC in attenuating Der p-induced airway inflammation. The results showed that NGF and TH2 related cytokines create an amplification loop resulting in broader allergic inflammation in upper-airway epithelial cells. In addition, WSC attenuated allergic inflammation and the epithelial cells damage through inhibiting NGF biosynthesis during allergic TH2 immune responses. In summary, we have demonstrated the role of NGF in a mouse model of house dust mite-induced AR, and the therapeutic effect of WSC in our AR mouse model, may through the attenuation NGF-induced airway inflammation as well as the inhibition of NGF synthesis. Our finding provides a new therapeutic modality of patients suffered with AR in clinical condition.
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