Expression of growth factors by airway epithelial cells in a model of chronic asthma: regulation and relationship to subepithelial fibrosis
Expression of growth factors by airway epithelial cells in a model of chronic asthma: regulation and relationship to subepithelial fibrosis
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DOI：
10.1111/j.1365-2222.2004.1917.x
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发表时间：
2004-04-01
影响因子：
6.1
通讯作者：
Foster, PS
中科院分区：
文献类型：
--
作者：
Kumar, RK;Herbert, C;Foster, PS
背景气道上皮细胞产生的生长因子可能在上皮下纤维化的发病机制中起重要作用，目的探讨肺上皮下纤维化的发生与转化生长因子β 1（TGF β 1）表达的关系（TGF-β 1）和表皮生长因子受体的配体。对卵清蛋白致敏的c小鼠通过吸入低水平的抗原进行慢性攻击，导致上皮下纤维化的发展和气道壁重塑的其他变化。生长因子的表达进行了评估，免疫组化和酶immunoassociation.Results过敏致敏直接与气道上皮细胞表达的裂解，潜在的生物活性形式的TGF-β 1和双调蛋白在过敏原的挑战。TGF-β 1的积累与慢性哮喘气道壁的重塑有关，而双调蛋白的表达没有表现出类似的关系。上皮细胞来源的TGF-β 1的产生似乎受到IL-13的调节，而IL-13和CD 4（+）T细胞都调节TGF-β 1的积累。结论气道上皮细胞源性TGF-β 1在哮喘气道重塑中可能起重要作用。免疫机制可能调节TGF-β 1的释放和积累。
Background Growth factors produced by airway epithelial cells may be important in the pathogenesis of subepithelial fibrosis, a distinctive lesion of chronic human asthma.Objective To examine the relationship between the development of subepithelial fibrosis and the expression of transforming growth factor-beta1 (TGF-beta1) and ligands for the epidermal growth factor receptor.Methods BALB/c mice sensitized to ovalbumin were chronically challenged by inhalation of low levels of antigen, leading to development of subepithelial fibrosis and other changes of airway wall remodelling. Growth factor expression was assessed by immunohistochemistry and enzyme immunoassay.Results Allergic sensitization directly correlated with airway epithelial expression of both the cleaved, potentially biologically active form of TGF-beta1 and of amphiregulin in response to allergen challenge. Accumulation of TGF-beta1 was related to remodelling of the airway wall in chronic asthma, whereas expression of amphiregulin did not exhibit a similar relationship. Production of epithelial cell-derived TGF-beta1 appeared to be regulated by IL-13, while both IL-13 and CD4(+) T cells regulated accumulation of TGF-beta1. In contrast to results reported in high-level exposure models of airway fibrosis, eosinophils did not appear to be a significant source of TGF-beta1.Conclusion Airway epithelial cell-derived TGF-beta1 has a potentially crucial role in the development of airway wall remodelling in asthma. Immunological mechanisms may regulate the release and accumulation of TGF-beta1.