Cigarette smoking increases bronchial mucosal IL-17A expression in asthmatics, which acts in concert with environmental aeroallergens to engender neutrophilic inflammation

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Abstract

BACKGROUND: Mild asthmatics who smoke cigarettes may develop unstable disease and neutrophilic infiltration of the airways, features more usually associated with severe asthmatic disease. The mechanisms giving rise to this response remain unclear.

OBJECTIVE: To address the hypothesis that smoking increases bronchial mucosal production of IL-17A which acts on bronchial epithelial cells directly and in concert with other environmental stimuli to induce the production of IL-6 and neutrophil chemotaxins.

METHODS: IL-17A, IL-8, IL-6, neutrophils and eosinophils was detected and quantified by immunohistochemistry in endobronchial biopsy sections from smoking and non-smoking asthmatics. Human tracheal epithelial cells (HTEpC) were cultured with IL-17A in the presence/absence of cigarette smoke extract (CSE) and aeroallergens lacking intrinsic protease activity, and IL-6 and IL-8 production measured in vitro.

RESULTS: Expression of IL-17A, IL-6 and IL-8 and neutrophil numbers were significantly elevated in the bronchial mucosa of the asthmatic smokers compared to the non-smokers. Expression of IL-17A correlated with that of IL-8 and neutrophil numbers. In the smoking asthmatics, eosinophil numbers also correlated with expression of IL-8 and IL-17A. Exposure of HTEpC cells to both CSE and IL-17A increased expression of IL-6 and IL-8 in a concentration-dependent and synergistic manner. Co-stimulation with CSE, IL-17A and aeroallergens further increased IL-6 and IL-8 production synergistically.

CONCLUSIONS: The data support the hypothesis that asthmatic smokers develop neutrophilic inflammation of the airways propagated at least partly by smoke-induced production of IL-17A which together with smoke and other environmental stimuli acts on airways epithelial cells to induce neutrophil chemotaxins. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)740-750
JournalClinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
Volume47
Issue number6
Early online date17 Feb 2017
DOIs
Publication statusPublished - 30 Jun 2017

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