title: Cigarette smoking increases bronchial mucosal IL-17A expression in asthmatics, which acts in concert with environmental aeroallergens to engender neutrophilic inflammation.
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 were 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 was 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.
authors.affiliation: Division of Asthma, Allergy and Lung Biology, MRC-Asthma UK Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, UK.
authors.forename: L Q C
authors.identifier: http://orcid.org/0000-0003-3656-939X
authors.initials: LQC
authors.lastname: Siew
authors.affiliation: Division of Asthma, Allergy and Lung Biology, MRC-Asthma UK Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, UK.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Division of Asthma, Allergy and Lung Biology, MRC-Asthma UK Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Ying
authors.affiliation: Division of Asthma, Allergy and Lung Biology, MRC-Asthma UK Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Corrigan
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000276:immunology / Q000473:pathology; D000073865:Cigarette Smoking / Q000009:adverse effects* / Q000276:immunology; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D020381:Interleukin-17 / Q000096:biosynthesis*; D020556:Neutrophil Infiltration / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: D000485:Allergens; D020381:Interleukin-17
keywords: aeroallergen; asthma; cigarette smoking; endobronchial biopsies; interleukin-17A