The role of fibroblast and Toll-like receptor in asthma animal model

Autor: Jang Fang-Yi, 鄭芳怡
Rok vydání: 2007
Druh dokumentu: 學位論文 ; thesis
Popis: 94
Allergic asthma is an inflammatory disease of bronchial airways. When allergens contact with lung tissue, the innate immune response was initiated, subsequently, leaded to inflammatory cells accumulation and chemokine secretion, and finally resulted in Th2 immune development. There are four major cell types in lung tissue including epithelial cells, fibroblasts, macrophages, and endothelial cells. In order to study the mechanism of innate immunity in the asthma disease, we intratrachealy administrated allergens into C57BL/6 mice for seven days then to evaluate the infiltrated cells in bronchial alveolar lavage fluids (BALF). We found that eosinophils and lymphocytes respectively accumulated in ovalbumin (OVA)- and recombinant Dermatophagoide peteronyssinus (rDer p2)-treated mice, indicating that lung epithelium shortly stimulated by allergens caused to airway inflammation. Furthermore, primary lung fibroblasts stimulated with OVA or rDer p2 secreted higher levels of RANTES, eotaxin, TNF-a, and TGF-b. Interestingly, elevated levels of the thymic stromal cell-derived lymphopoietin (TSLP) and nerve growth factor (NGF) also detected in OVA- or rDer p2-treated groups. Finally, we use neutralizing assay to evaluate whether the toll-like receptor (TLR) involved in this phenomena. We found that using anti-TLR2 and anti-TLR4 antibodies could dose-dependently inhibited TNF-a secretion by rDer p2 stimulation, moreover. C3H/HeJ mice secreted significantly lower level of TNF-a compared to C3H/HeN mice. Summarizing the above data, TLR2 and TLR4 both involved in the cytokine secretion by rDer p2 stimulation. To study the role of lung fibroblasts on the airway sensitizing stage will contribute to more clear realization of the innate immune response in asthma disease.
Databáze: Networked Digital Library of Theses & Dissertations
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