IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines

作者：Sophie Molet, Qutayba A. Hamid, Francis Davoineb, Esra Nutku, Rame Tahaa, Nathalie Pagé, Ron Olivenstein, Jack Angel Elias, Jamila Chakir · 发表于：Journal of Allergy and Clinical Immunology · 年份：2001 · DOI：10.1067/mai.2001.117929 · 被引用次数：963 · 研究领域：Psoriasis: Treatment and Pathogenesis、Asthma and respiratory diseases、Dermatology and Skin Diseases

BACKGROUND: IL-17 is a cytokine that has been reported to be produced by T lymphocytes. In vitro, IL-17 activates fibro-blasts and macrophages for the secretion of GM-CSF, TNF-alpha, IL-1beta, 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 bi...