Dabbagh K, Takeyama K, Lee H M, Ueki I F, Lausier J A, Nadel J A
Cardiovascular Research Institute and Departments of Medicine and Physiology, University of California, San Francisco, CA 94143, USA.
J Immunol. 1999 May 15;162(10):6233-7.
Goblet cell metaplasia and mucus hypersecretion are important features in the pathogenesis of asthma. The cytokine IL-4 has been shown to play a role in animal models of asthma, where it induces Th2 lymphocyte differentiation and B lymphocyte IgE class switch. IL-4 has also been implicated in the differentiation of goblet cells via effects on lymphocytes and eosinophils. In this study we hypothesized that IL-4 induces airway epithelial cell mucin gene expression and mucous glycoconjugate production by direct action on these cells. In vitro, cultured airway epithelial cells (NCI-H292) expressed IL-4R constitutively, and IL-4 (10 ng/ml) induced MUC2 gene expression and mucous glycoconjugate production. In vivo, mouse airway epithelial cells expressed IL-4R constitutively, and IL-4 (250 ng) increased MUC5 gene expression and Alcian blue/periodic acid-Schiff-positive staining at 24 h; IL-4 did not increase inflammatory cell numbers in airway tissue or in bronchoalveolar lavage. TNF-alpha and IL-1beta levels in bronchoalveolar lavage were not increased in response to IL-4 instillation. These results indicate that airway epithelial cells express IL-4R constitutively and that IL-4 directly induces the differentiation of epithelium into mucous glycoconjugate-containing goblet cells.
杯状细胞化生和黏液分泌亢进是哮喘发病机制中的重要特征。细胞因子白细胞介素 -4（IL-4）已被证明在哮喘动物模型中发挥作用，它可诱导Th2淋巴细胞分化和B淋巴细胞IgE类别转换。IL-4还通过对淋巴细胞和嗜酸性粒细胞的作用参与杯状细胞的分化。在本研究中，我们假设IL-4通过直接作用于气道上皮细胞来诱导其黏蛋白基因表达和黏液糖缀合物的产生。在体外，培养的气道上皮细胞（NCI-H292）组成性表达IL-4受体，IL-4（10 ng/ml）可诱导MUC2基因表达和黏液糖缀合物的产生。在体内，小鼠气道上皮细胞组成性表达IL-4受体，IL-4（250 ng）在24小时时增加MUC5基因表达和阿利新蓝/过碘酸希夫氏阳性染色；IL-4并未增加气道组织或支气管肺泡灌洗中的炎性细胞数量。支气管肺泡灌洗中的肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平在给予IL-4滴注后并未升高。这些结果表明气道上皮细胞组成性表达IL-4受体，且IL-4可直接诱导上皮细胞分化为含黏液糖缀合物的杯状细胞。
