Airway cell involvement in intermittent hypoxia-induced airway inflammation

• Published in: Sleep & breathing Vol. 19; no. 1; pp. 297 - 306
• Main Authors: Philippe, C., Boussadia, Y., Prulière-Escabasse, V., Papon, J F., Clérici, C., Isabey, D., Coste, A., Escudier, E., d’Ortho, M P.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2015; Springer Nature B.V; Springer Verlag
• Subjects: Adult; Cells; Dentistry; Epithelial Cells; Epithelial Cells - physiology; Genetics; Human genetics; Human health and pathology; Humans; Hypoxia; Hypoxia - physiopathology; In Vitro Techniques; Inflammation Mediators; Inflammation Mediators - metabolism; Internal Medicine; Life Sciences; Medicine; Medicine & Public Health; Myocytes, Smooth Muscle; Myocytes, Smooth Muscle - physiology; Neurology; Original Article; Otorhinolaryngology; Pediatrics; Pneumology/Respiratory System; Pulmonology and respiratory tract; Respiratory Mucosa; Respiratory Mucosa - physiopathology; Sleep apnea; Sleep Apnea, Obstructive; Sleep Apnea, Obstructive - physiopathology; Neutrophil migration; Obstructive sleep apnea syndrome; Airway epithelial cells; Airway smooth muscle cells
• ISSN: 1520-9512; 1522-1709
• DOI: 10.1007/s11325-014-1019-4

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.