van der Velden V H, Naber B A, Wierenga-Wolf A F, Debets R, Savelkoul H F, Overbeek S E, Hoogsteden H C, Versnel M A
Department of Immunology, Erasmus University and University Hospital Dijkzigt, Rotterdam, The Netherlands.
Cytokine. 1998 Oct;10(10):803-13. doi: 10.1006/cyto.1998.0365.
Asthma is considered a Th2-like disease, characterized by locally increased levels of interleukin (IL) 4. The bronchial epithelium plays an important role in the initiation and perpetuation of inflammatory reactions within the airways. However, little is known about the presence of IL-4 receptors on human bronchial epithelial cells, or the effects of IL-4 on these cells. In this report, definitive evidence of IL-4 receptor expression on human bronchial epithelial cells using several methods is presented. IL-4 receptor expression on human bronchial epithelial cells in vivo was demonstrated using in situ hybridization and immunohistochemistry. No difference in IL-4 receptor protein expression was observed between bronchial biopsies of healthy subjects compared to allergic asthmatics. Cultured human bronchial epithelial cells also expressed IL-4 receptor mRNA and protein (as determined by RT-PCR analysis and flow cytometry, respectively). IL-4 receptor protein expression by bronchial epithelial cells could be increased by stimulation with PMA+calcium ionophore, whereas IL-1beta and IL-6 decreased IL-4 receptor expression. A cyclic AMP analogue and IL-4 had no effect. Finally, it is shown that the IL-4 receptor is functionally active as IL-4 stimulates the release of IL-8, monocyte chemoattractant protein 1, and particularly IL-1 receptor antagonist by human bronchial epithelial cells. It is concluded that human bronchial epithelial cells express IL-4 receptors both in vivo and in vitro. Stimulation of human bronchial epithelial cells by IL-4 may result in the release of both pro- and anti-inflammatory mediators known to be upregulated in asthmatic airways.
哮喘被认为是一种类似Th2的疾病，其特征是局部白细胞介素（IL）-4水平升高。支气管上皮在气道内炎症反应的起始和持续中起重要作用。然而，关于人支气管上皮细胞上IL-4受体的存在情况，或IL-4对这些细胞的影响，人们了解甚少。在本报告中，使用多种方法提供了人支气管上皮细胞上IL-4受体表达的确切证据。通过原位杂交和免疫组织化学证明了体内人支气管上皮细胞上的IL-4受体表达。与过敏性哮喘患者相比，健康受试者的支气管活检中未观察到IL-4受体蛋白表达的差异。培养的人支气管上皮细胞也表达IL-4受体mRNA和蛋白（分别通过逆转录-聚合酶链反应分析和流式细胞术确定）。支气管上皮细胞的IL-4受体蛋白表达可通过佛波酯+钙离子载体刺激而增加，而IL-1β和IL-6则降低IL-4受体表达。环磷酸腺苷类似物和IL-4没有作用。最后，结果表明IL-4受体具有功能活性，因为IL-4刺激人支气管上皮细胞释放IL-8、单核细胞趋化蛋白1，特别是IL-1受体拮抗剂。结论是人支气管上皮细胞在体内和体外均表达IL-4受体。IL-4对人支气管上皮细胞的刺激可能导致已知在哮喘气道中上调的促炎和抗炎介质的释放。
