title: IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines.
abstract: 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 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 alpha-chemokines, IL-8, and growth-related oncogene-alpha.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Molet
authors.forename: Q
authors.initials: Q
authors.lastname: Hamid
authors.forename: F
authors.initials: F
authors.lastname: Davoine
authors.forename: E
authors.initials: E
authors.lastname: Nutku
authors.forename: R
authors.initials: R
authors.lastname: Taha
authors.forename: N
authors.initials: N
authors.lastname: Pagé
authors.forename: R
authors.initials: R
authors.lastname: Olivenstein
authors.forename: J
authors.initials: J
authors.lastname: Elias
authors.forename: J
authors.initials: J
authors.lastname: Chakir
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism*; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D017370:Interleukin-11 / Q000378:metabolism; D020381:Interleukin-17 / Q000302:isolation & purification / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D013183:Sputum / Q000276:immunology
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D016207:Cytokines; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D017370:Interleukin-11; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8