PURPOSE: 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.
PURPOSE: 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: A Coste; L Brugel; B Maître; S Boussat; J F Papon; L Wingerstmann; R Peynègre; E Escudier Journal: Eur Respir J Date: 2000-02 Impact factor: 16.671
Authors: Giovanna E Carpagnano; Sergei A Kharitonov; Onofrio Resta; Maria P Foschino-Barbaro; Enzo Gramiccioni; Peter J Barnes Journal: Chest Date: 2002-10 Impact factor: 9.410
Authors: Giovanna E Carpagnano; Antonio Spanevello; Roberto Sabato; Annarita Depalo; Grazia P Palladino; Laura Bergantino; Maria P Foschino Barbaro Journal: Transl Res Date: 2010-01 Impact factor: 7.012
Authors: F G Salerno; E Carpagnano; P Guido; M R Bonsignore; A Roberti; M Aliani; A M Vignola; A Spanevello Journal: Respir Med Date: 2004-01 Impact factor: 3.415
Authors: Cristen Pantano; Jennifer L Ather; John F Alcorn; Matthew E Poynter; Amy L Brown; Amy S Guala; Stacie L Beuschel; Gilman B Allen; Laurie A Whittaker; Mieke Bevelander; Charles G Irvin; Yvonne M W Janssen-Heininger Journal: Am J Respir Crit Care Med Date: 2008-02-08 Impact factor: 21.405
Authors: Eun Jung Lee; Woon Heo; Joo Young Kim; Hyungchul Kim; Min Jung Kang; Bo Ra Kim; Ji Hyun Kim; Do Yang Park; Chang-Hoon Kim; Joo-Heon Yoon; Hyung-Ju Cho Journal: Mediators Inflamm Date: 2017-09-06 Impact factor: 4.711