Source: International Congress 2014 – Different interesting issues in respiratory infections: 1
Disease area: Respiratory infections

Abstract

Acute and chronic infectious diseases of the respiratory tract, such as pneumonia and cystic fibrosis, are associated with mucosal and systemic hypoxia. Innate immune functions of respiratory epithelial cells are required to prevent and control infections of the lung. The transcription factor HIF-1a regulates cellular adaptation to low oxygen conditions. Here, we show that hypoxia and HIF-1a regulate innate immune mechanisms of cultured human bronchial epithelial cells (HBECs).Exposure of HBECs to hypoxia or the hypoxia-mimetic agent cobalt chloride (CoCl₂) resulted in a significantly decreased expression and release of inflammatory mediators (e.g. IL-6, IP-10) and the antimicrobial peptide hBD-2 in response to bacterial infection with P. aeruginosaand ligands for Toll-like receptors (flagellin, polyI:C). Small interfering RNA–mediated knockdown of the hypoxia-inducible factor 1a (HIF-1a) in HBECs resulted in increased expression of these factors under normoxic and hypoxic conditions. Hypoxia reduced the antimicrobial activity of HBECs against P. aeruginosa. The inflammatory response was decreased in lungs of mice infected with inactivated P. aeruginosa under hypoxia. These data suggest that hypoxia suppresses the innate immune response of respiratory epithelial cells via HIF-1 a.

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M. Polke, P. Lepper, A. Kamyschnikow, F. Langer, D. Monz, C. Herr, R. Bals, C. Beisswenger (Homburg (Saar), Germany). Hypoxia and the hypoxia-regulated transcription factor HIF-1alpha suppress the host defense of the respiratory epithelium. Eur Respir J 2014; 44: Suppl. 58, 2547

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