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Am J Physiol Lung Cell Mol Physiol 293: L69-L76, 2007. First published March 23, 2007; doi:10.1152/ajplung.00299.2006
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Bronchial epithelial cell growth regulation in fibroblast cocultures: the role of hepatocyte growth factor

Grzegorz Skibinski, J. Stuart Elborn, and Madeleine Ennis

Respiratory Medicine Research Cluster, School of Medicine and Dentistry, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom

Submitted 8 August 2006 ; accepted in final form 14 March 2007

Proliferation of bronchial epithelial cells is an important biological process in physiological conditions and various lung diseases. The objective of this study was to determine how bronchial fibroblasts influence bronchial epithelial cell proliferation. The proliferative activity in cocultures was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and direct cells counts. Concentration of cytokines was measured in cell culture supernatants by means of ELISA. In primary cell cocultures, fibroblasts or fibroblast-conditioned medium enhanced 1.85-fold the proliferation of primary bronchial epithelial cells (P < 0.02) compared with bronchial epithelial cells cultured alone. The proliferative activity in cocultures and in fibroblast-conditioned medium was reduced by neutralizing antibody to hepatocyte growth factor (HGF) and HGF receptor c-met. Neutralizing antibodies to FGF-7 and IGF-1 had no effect. Treatment of fibroblast-epithelial cocultures with anti-IL-6 and anti-TNF-{alpha} neutralizing antibodies and with indomethacin decreased production of HGF. These results indicate that cytokines and PGE2 may indirectly mediate epithelial cell proliferation via the regulation of HGF in bronchial stromal cells and that HGF plays a crucial role in proinflammatory cytokine-induced proliferation in the experimental system studied.

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Address for reprint requests and other correspondence: G. Skibinski, Respiratory Medicine Research Cluster, Institute of Clinical Science, Queen's Univ., Grosvenor Rd., Belfast BT12 6BJ, Northern Ireland, United Kingdom (e-mail: G.Skibinski{at}qub.ac.uk)






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