Potential action of IL-4 and IL-13 as fibrogenic factors on lung fibroblasts in vitro
Potential action of IL-4 and IL-13 as fibrogenic factors on lung fibroblasts in vitro
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DOI：
10.1159/000073718
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发表时间：
2003-10-01
影响因子：
2.8
通讯作者：
Takizawa, H
中科院分区：
文献类型：
--
作者：
Saito, A;Okazaki, H;Takizawa, H
背景：哮喘的特征是以Th2细胞因子存在的慢性呼吸道炎症为特征。哮喘的气道重塑与临床表现密切相关。肺肌成纤维细胞在气道重塑中起重要作用，Th2细胞因子可能对其行为起调节作用。我们检测了两种主要的Th2细胞因子IL-4和IL-13对肺成纤维细胞向肌成纤维细胞分化的影响。我们假设这些细胞因子会刺激成纤维细胞的增殖，并伴随前列腺素E-2(PGE(2))的降低。方法：体外培养肺成纤维细胞，分别加入IL-4、IL-13和Th1细胞因子干扰素-γ。肺成纤维细胞分化为肌成纤维细胞的特征是α-平滑肌肌动蛋白(α-SMA)的表达以及形态和免疫组织化学分析。用四甲基偶氮唑盐比色法检测IL-4和IL-13对成纤维细胞增殖的影响。我们还研究了这些细胞因子对环氧合酶(COX)基因表达和PGE(2)产生的影响。结果：IL-4和IL-13促进α-SMA表达和肌成纤维细胞分化。此作用可被干扰素-γ减弱，地塞米松对分化无影响。IL-4和IL-13刺激成纤维细胞增殖。这些细胞因子下调COX-1和COX-2基因的表达，减少PGE(2)的产生。结论：IL-4和IL-13可诱导成纤维细胞向肌成纤维细胞分化，此作用可被干扰素-γ减弱。IL-4和IL-13刺激成纤维细胞增殖，这种作用至少部分是由于抑制了COX基因的表达，从而减少了PGE(2)的产生。提示IL-4和IL-13直接作用于肺成纤维细胞，诱导纤维化反应。版权所有(C)2003 S.Karger AG，巴塞尔。
Background: 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. Lung myofibroblasts play a critical role in the airway remodeling and Th2 cytokines may modulate their behavior. We examined the effect of two major Th2 cytokines, IL-4 and IL-13, on differentiation of lung fibroblasts to myofibroblasts. We hypothesized that these cytokines would stimulate fibroblast proliferation in association with decreased prostaglandin E-2 (PGE(2)). Methods: Lung fibroblasts were incubated with IL-4 and IL-13 with or without Th1 cytokine interferon-gamma (IFN-gamma) in vitro. Differentiation of lung fibroblasts to myofibroblasts was characterized by the expression of alpha-smooth muscle actin (alpha-SMA) as well as a morphological and immunohistochemical analysis. Fibroblast proliferation stimulated by IL-4 and IL-13 was assessed with the MTT assay. We also investigated the effect of these cytokines on cyclooxygenase (COX) gene expression and PGE(2) production. Results: IL-4 and IL-13 increased alpha-SMA expression and myofibroblastic differentiation. This effect was attenuated by IFN-gamma and dexamethasone failed to have an influence on differentiation. IL-4 and IL-13 stimulated fibroblast proliferation. These cytokines downregulated the expression of both COX-1 and COX-2 genes and decreased the production of PGE(2). Conclusions: IL-4 and IL-13 induce differentiation of fibroblasts to myofibroblasts and this response is attenuated by IFN-gamma. IL-4 and IL-13 stimulate fibroblast proliferation and this effect is at least partly due to suppressed COX gene expressions and subsequently decreased PGE(2) production. These findings suggest that IL-4 and IL-13 directly act on lung fibroblast to induce a fibrogenic response. Copyright (C) 2003 S. Karger AG, Basel.