IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines
IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines
复制标题
DOI：
10.1067/mai.2001.117929
复制
发表时间：
2001-09-01
影响因子：
14.2
通讯作者：
Chakir, J
中科院分区：
文献类型：
--
作者：
Molet, S;Hamid, Q;Chakir, J
背景：IL-17是一种由T淋巴细胞产生的细胞因子。在体外，IL-17激活成纤维细胞和巨噬细胞以分泌GM-CSF、TNF-α、IL-1 β和IL-6。目的：探讨哮喘患者痰液和支气管肺泡灌洗液中IL-17的表达，并与正常对照组比较。方法：采用免疫细胞化学、原位杂交和Western blot方法检测IL-17在哮喘患者痰液和支气管肺泡灌洗液中的表达。用IL-17刺激支气管成纤维细胞，并通过ELISA和RT-PCR.Results检测细胞因子和趋化因子的产生：使用免疫细胞化学，我们证明，与对照组相比，哮喘受试者的痰液和支气管肺泡灌洗液中IL-17阳性细胞的数量显著增加（分别为P < .001和P < .005）。我们证明，除了T细胞，嗜酸性粒细胞在痰液和支气管肺泡灌洗液表达IL-17。外周血嗜酸性粒细胞也呈IL-17阳性，哮喘患者外周血嗜酸性粒细胞中IL-17水平显著高于对照组（P <0.01）。为了进一步研究IL-17在体内的作用机制，我们检测了这种细胞因子对从哮喘和非哮喘受试者的支气管活检中分离的成纤维细胞的作用。IL-17确实增强成纤维细胞产生促纤维化细胞因子（IL-6和IL-11），而地塞米松可抑制这一作用。同样，IL-17增加了其他成纤维细胞源性炎症介质的水平，例如α-趋化因子、IL-8和生长相关癌基因-oc。结论：我们的研究结果首次证明嗜酸性粒细胞是哮喘气道内IL-17的潜在来源，提示IL-17可能具有通过释放促炎介质如α-趋化因子来放大炎症反应的潜力。
Background: IL-17 is a cytokine that has been reported to be produced by T lymphocytes. In vitro, IL-17 activates fibroblasts and macrophages for the secretion of GM-CSF, TNF-alpha, IL-1 beta, and IL-6. A number of these cytokines are involved in the airway remodeling that is observed within the lungs of asthmatic individuals.Objective: In this study, we investigated the expression of IL-17 in sputum and bronchoalveolar lavage specimens obtained from asthmatic subjects and from nonasthmatic control subjects.Methods: IL-17 was detected through use of immunocytochemistry, in situ hybridization, and Western blot. Bronchial fibroblasts were stimulated with IL-17, and cytokine production and chemokine production were detected through use of ELISA and RT-PCR.Results: Using immunocytochemistry, we demonstrated that the numbers of cells positive for IL-17 are significantly increased in sputum and bronchoalveolar lavage fluids of subjects with asthma in comparison with control subjects (P < .001 and P < .005, respectively). We demonstrated that in addition to T cells, eosinophils in sputum and bronchoalveolar lavage fluids expressed IL-17. Peripheral blood eosinophils were also positive for IL-17, and the level of IL-17 in eosinophils purified from peripheral blood was significantly higher in subjects with asthma than in controls (P < .01). To further investigate the mechanism of action of IL-17 in vivo, we examined the effect of this cytokine on fibroblasts isolated from bronchial biopsies of asthmatic and nonasthmatic subjects. IL-17 did enhance the production of profibrotic cytokines (IL-6 and IL-11) by fibroblasts, and this was inhibited by dexamethasone. Similarly, IL-17 increased the level of other fibroblast-derived inflammatory mediators, such as the alpha -chemokines, IL-8, and growth-related oncogene-oc.Conclusion: Our results, which demonstrate for the first time that eosinophils are a potential source of IL-17 within asthmatic airways, suggest that IL-17 might have the potential to amplify inflammatory responses through the release of proinflammatory mediators such as alpha -chemokines.