title: TH17 cytokines induce human airway smooth muscle cell migration.
abstract: BACKGROUND
  Migration of airway smooth muscle cells (ASMCs) might contribute to increased airway smooth muscle mass in asthma. T(H)17 cells and T(H)17-associated cytokines are involved in the pathogenesis of asthma and might also contribute to airway remodeling.
  
  
  OBJECTIVE
  We sought to explore the possibility that migration of ASMCs might contribute to airway remodeling through the action of T(H)17-related cytokines.
  
  
  METHODS
  The effect of exogenous T(H)17 cytokines on ex vivo human ASMC migration was investigated by using a chemotaxis assay. The involvement of signaling pathways, including p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 MAPK, nuclear factor κB, and phosphoinositide 3-kinase, was also examined.
  
  
  RESULTS
  We demonstrated that IL-17A, IL-17F, and IL-22 promote migration in a dose-dependent manner. We further demonstrated that ASMCs express receptors for IL-17RA, IL-17RC, and IL-22R1. Using mAbs directed against these receptors, we confirmed that T(H)17-associated cytokine-induced migration was dependent on selective receptor activation. Moreover, IL-17A and IL-17F exert their effects through signaling pathways that are distinct from those used by IL-22. The p38 MAPK inhibitor BIRB0796 inhibited the migration induced by IL-17A and IL-17F. PS1145, an inhibitor of nuclear factor κB, abolished the IL-22-induced migration.
  
  
  CONCLUSIONS
  These data raise the possibility that T(H)17-associated cytokines promote human ASMC migration in vivo and suggest an important new mechanism for the promotion of airway remodeling in asthma.
authors.affiliation: Meakins-Christie Laboratories and Respiratory Division, Department of Medicine McGill University, Montreal, Quebec, Canada.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chang
authors.forename: Laila
authors.initials: L
authors.lastname: Al-Alwan
authors.forename: Paul-André
authors.initials: PA
authors.lastname: Risse
authors.forename: Lucie
authors.initials: L
authors.lastname: Roussel
authors.forename: Simon
authors.initials: S
authors.lastname: Rousseau
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Halayko
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
authors.forename: David H
authors.initials: DH
authors.lastname: Eidelman
mesh_terms: D056151:Airway Remodeling / Q000502:physiology*; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D002465:Cell Movement / Q000502:physiology*; D002469:Cell Separation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines