Source: International Congress 2014 – Cell biology 2014
Disease area: Airway diseases

Abstract

For oxygen supply, airway wall cells depend on diffusion though the basement membrane, as well as on delivery by micro-vessels. In the asthmatic lung, local hypoxic conditions may occur due to increased thickness and altered composition of the basement membrane, as well as due to edema of the inflamed airway wall.We investigated the effect of hypoxia on proliferation, pro-inflammatory and pro-angiogenic parameters of human bronchial smooth muscle cells (BSMC). BSMC were cultured in RPMI1640 (5% FCS) under normoxic (21% O2) and hypoxic (1% and 5% O2) conditions. Proliferation was determined by cell count and Western blot analysis for cyclin E and Proliferating Cell Nuclear Antigen (PCNA). Levels of IL-6, IL-8, ENA-78 and VEGF-A were analyzed by ELISA. BSMC conditioned medium was tested for its angiogenic capacity by endothelial cell (EC)-spheroid in vitro angiogenesis assay.Proliferation of BSMC from asthmatics and non-asthmatics was significantly reduced in the presence of 1% O2, whereas 5% O2 reduced proliferation of asthmatic BSMC only. Hypoxia induced HIF-1a expression in asthmatic and non-asthmatic BSMC, and significantly increased release of IL-6, IL-8 and VEGF-A, but not ENA-78. Endothelial sprout outgrowth from EC spheroids was increased when exposed to hypoxia conditioned BSMC medium.We conclude that hypoxia exerts dualistic effects on proliferative and inflammatory responses of asthmatic and non-asthmatic BSMC. First, hypoxia reduced BSMC proliferation. Second, hypoxia induced a pro-inflammatory, pro-angiogenic response. BSMC and EC may thus be promising new targets to counteract and/or alleviate airway wall remodeling.

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Citations should be made in the following way:
L. Keglowich, M. Tamm, P. Borger (Basel, Switzerland). Hypoxia exerts dualistic effects on inflammatory and proliferative responses of healthy and asthmatic primary human bronchial smooth muscle cells. Eur Respir J 2014; 44: Suppl. 58, 3844

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