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

• Published in: Journal of allergy and clinical immunology Vol. 108; no. 3; pp. 430 - 438
• Main Authors: Molet, Sophie, Hamid, Qutayba, Davoineb, Francis, Nutku, Esra, Tahaa, Rame, Pagé, Nathalie, Olivenstein, Ron, Elias, Jack, Chakir, Jamila
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.09.2001; Elsevier
• Subjects: a-Chemokines; Adult; Allergic diseases; Asthma; Asthma - immunology; Biological and medical sciences; Bronchi - cytology; Bronchi - drug effects; Bronchoalveolar Lavage Fluid - immunology; Chemokine CXCL1; Chemokines, CXC; Chemotactic Factors - biosynthesis; Chronic obstructive pulmonary disease, asthma; cytokines; Cytokines - secretion; eosinophils; Eosinophils - immunology; Female; fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Growth Substances - biosynthesis; Humans; Immunopathology; Intercellular Signaling Peptides and Proteins; Interleukin-11 - secretion; Interleukin-17 - isolation & purification; Interleukin-17 - pharmacology; Interleukin-6 - secretion; Interleukin-8 - biosynthesis; Male; Medical sciences; Pneumology; remodeling; Respiratory and ent allergic diseases; Sputum - immunology; remodeling; TBS; BAF; ICC; eosinophils; BAL; ECM; Asthma; fibroblasts; TGF; Dex; Gro-α; cytokines; MBP; BNF; Human; Immunopathology; Allergy; Respiratory disease; Pathogenesis; Cytokine; Granulocyte; Inflammation; Remodeling; Eosinophil; Interleukin 17; Chemokine; Respiratory tract; Bronchoalveolar lavage; Sputum; Obstructive pulmonary disease; Fibroblast
• ISSN: 0091-6749
• DOI: 10.1067/mai.2001.117929

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-α, IL-1β, 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 pro-fibrotic 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 α-chemokines, IL-8, and growth-related oncogene-α. 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 α-chemokines. (J Allergy Clin Immunol 2001;108:430-8.)