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1 Respiratory Medicine Research Cluster, Queen's University, Belfast, Northern, Ireland, United Kingdom
* To whom correspondence should be addressed. E-mail: g.skibinski{at}qub.ac.uk.
Abstract
Proliferation of bronchial epithelial cells is an important biologic process in physiologic 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 co-cultures was assessed by MTT assay and direct cells counts. Concentration of cytokines was measured in cell culture supernatants by means of ELISA. In primary cell co-cultures, fibroblasts or fibroblast conditioned medium enhanced 1.85 fold the proliferation of primary bronchial epithelial cells (p<0.02) in comparison to bronchial epithelial cells coultured alone. The proliferative activity in co-cultures and in fibroblast-conditioned medium was reduced by neutralizing antibody to HGF and HGF receptor c-met. Neutralizing antibodies to FGF7 and IGF1 had no effect. Treatment of fibroblast/epithelial co-cultures with anti-IL-6 and anti-TNF
neutralising antibodies and with indomethacine decreased production of HGF. These results indicate that pro-inflammatory 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 epithalial cell proliferation in the experimental system studied.
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