Interactions of myofibroblasts with airway epithelial cells in allergic airway inflammation

哮喘的特征是慢性呼吸道炎症和Th2细胞因子的存在。哮喘的气道重塑与临床表现密切相关。肺成纤维细胞在气道重塑中起关键作用，Th2细胞因子可调节其行为。肺成纤维细胞与IL-4和IL-13共同孵育。对正常肺成纤维细胞向肌成纤维细胞的分化进行了形态和免疫组织化学分析，并检测了α-突触肌动蛋白(α-SMA)的表达。我们进一步研究了细胞因子干扰素γ(干扰素-γ)的作用。用四甲基偶氮唑盐比色法检测成纤维细胞的增殖情况。IL-4和IL-13促进α-SMA表达和肌成纤维细胞分化，这种作用可被TFW-γ减弱。IL-4和IL-13刺激成纤维细胞增殖。这些细胞因子下调COX-L和COX-2基因的表达，减少PGE2的产生，IL-4和IL-13诱导成纤维细胞向肌成纤维细胞分化。干扰素-γ可减弱这种反应，但地塞米松不能影响分化。IL-4和IL-13刺激成纤维细胞增殖，其作用至少部分是由于抑制了COX基因的表达，从而减少了PGE2的产生。提示Th2细胞因子IL-4和IL-13直接作用于肺成纤维细胞，诱导成纤维细胞反应。

Asthma is characterized by chronic inflammation of the airway with the presence of Th2 cytokines. Airway remodeling in asthma is, closely related to clinical manifestations. hung myofibroblasts play a critical role,in the airway remodeling and Th2 cytokines may modulate their behavior.Lung fibroblasts were incubated with IL-4 and IL-13 in vitro. Differentiation of normal lung fibroblasts to myofibroblasts was characterized by the expression of a-sniooth muscle actin (α-SMA) as well as morphologic and immunohistochemical analysis. We further studied the effect of a Thi cytokine interferonγ(IFN-γ). Fibroblast proliferation was assessed by MTT assay. We also investigated the effect of these cytokines on cyclooxygenase (COX) gene expression and PGE_2 production.IL-4 and IL-13 increased α-SMA expression and myofibroblastic differentiation and, this effect was attenuated by TFW-γ. IL-4 and IL-13 stimulated fibroblast proliferation. These cytokines downregulated the expression of both COX-l and COX-2 genes and decreased the production of PGE_2.IL-4 arid IL-13 induce differentiation of fibroblasts to myofibroblasts. IFN-γ attenuates this response, but dexamethasone fails to influence on differentiation. IL-4 and IL-13 stimulate fibroblast proliferation and this effect is at least partly due to suppressed COX genes expressions and subsequently decreased PGE_2.production. These findings suggest that Th2 cytokines IL-4 and IL-13 directly act on lung fibroblast to induce fibrocjenic responses.