Kumar R K, Herbert C, Foster P S
Department of Pathology, University of New South Wales, Sydney, Australia.
Clin Exp Allergy. 2004 Apr;34(4):567-75. doi: 10.1111/j.1365-2222.2004.1917.x.
Growth factors produced by airway epithelial cells may be important in the pathogenesis of subepithelial fibrosis, a distinctive lesion of chronic human asthma.
To examine the relationship between the development of subepithelial fibrosis and the expression of transforming growth factor-beta 1 (TGF-beta 1) and ligands for the epidermal growth factor receptor.
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.
Allergic sensitization directly correlated with airway epithelial expression of both the cleaved, potentially biologically active form of TGF-beta 1 and of amphiregulin in response to allergen challenge. Accumulation of TGF-beta 1 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-beta 1 appeared to be regulated by IL-13, while both IL-13 and CD4(+) T cells regulated accumulation of TGF-beta 1. In contrast to results reported in high-level exposure models of airway fibrosis, eosinophils did not appear to be a significant source of TGF-beta 1.
Airway epithelial cell-derived TGF-beta 1 has a potentially crucial role in the development of airway wall remodelling in asthma. Immunological mechanisms may regulate the release and accumulation of TGF-beta 1.
气道上皮细胞产生的生长因子可能在慢性人类哮喘的特征性病变——上皮下纤维化的发病机制中起重要作用。
研究上皮下纤维化的发展与转化生长因子-β1（TGF-β1）表达及表皮生长因子受体配体之间的关系。
对卵清蛋白致敏的BALB/c小鼠通过吸入低水平抗原进行慢性激发，导致上皮下纤维化及气道壁重塑的其他变化。通过免疫组织化学和酶免疫测定评估生长因子表达。
变应原激发后，变应性致敏与气道上皮中裂解的、具有潜在生物活性形式的TGF-β1及双调蛋白的表达直接相关。TGF-β1的积聚与慢性哮喘气道壁重塑有关，而双调蛋白的表达未表现出类似关系。上皮细胞源性TGF-β1的产生似乎受白细胞介素-13调节，而白细胞介素-13和CD4(+) T细胞均调节TGF-β1的积聚。与气道纤维化高水平暴露模型报道的结果相反，嗜酸性粒细胞似乎不是TGF-β1的重要来源。
气道上皮细胞源性TGF-β1在哮喘气道壁重塑的发展中可能起关键作用。免疫机制可能调节TGF-β1的释放和积聚。
