title: Airway cell involvement in intermittent hypoxia-induced airway inflammation.
abstract: OBJECTIVE
  Respiratory inflammation has been described in patients with obstructive sleep apnea syndrome, but it is unknown whether the increased neutrophil and interleukin (IL)-8 levels observed in induced sputum reflect systemic or local airway inflammation. We assessed the potential role of resident cells in intermittent hypoxia-induced airway inflammation.
  
  
  METHODS
  Airway epithelial cells (AEC) and bronchial smooth muscle cells (BSMC) were exposed to intermittent hypoxia (IH) in vitro. Cell supernatants were assessed for matrix metalloproteinase, growth factor, and cytokine expression. The role of IH on neutrophil and BSMC migration capacities was evaluated, and the effect of supernatants from IH-exposed or control AEC was tested.
  
  
  RESULTS
  Compared to normoxic conditions, 24 h of exposure to IH induced a significant increase of MMP-9 and MMP-2 expression and pro-MMP-9 activation (p < 0.05), and IL-8 (p < 0.05), platelet-derived growth factor (PDGF)-AA (p < 0.05), and vascular endothelial growth factor (VEGF) (p < 0.05) expression by AEC and VEGF expression (p = 0.04) by BSMC. Neutrophil chemotaxis and BSMC migration were enhanced by IH and supernatants of IH-exposed AEC (112.00 ± 4.80 versus 0.69 ± 0.43 %, p = 0.0053 and 247 ± 76 versus 21 ± 23, p = 0.009 respectively). This enhanced BSMC migration was totally abolished in the presence of an antibody blocking PDGF-AA.
  
  
  CONCLUSIONS
  These data suggest a specific inflammatory response of airway cells to IH, independently of systemic events.
authors.affiliation: INSERM, U955, Equipe 13, Créteil, France, carole.philippe@psl.aphp.fr.
authors.forename: C
authors.initials: C
authors.lastname: Philippe
authors.forename: Y
authors.initials: Y
authors.lastname: Boussadia
authors.forename: V
authors.initials: V
authors.lastname: Prulière-Escabasse
authors.forename: J F
authors.initials: JF
authors.lastname: Papon
authors.forename: C
authors.initials: C
authors.lastname: Clérici
authors.forename: D
authors.initials: D
authors.lastname: Isabey
authors.forename: A
authors.initials: A
authors.lastname: Coste
authors.forename: E
authors.initials: E
authors.lastname: Escudier
authors.forename: M P
authors.initials: MP
authors.lastname: d'Ortho
mesh_terms: D000328:Adult; D004847:Epithelial Cells / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D020545:Respiratory Mucosa / Q000503:physiopathology*; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*
chemical_list: D018836:Inflammation Mediators