Noncompetitive, chemokine-mediated inhibition of basic fibroblast growth factor-induced endothelial cell proliferation.

The Journal of Biological Chemistry
M PrestaR Horuk

Abstract

The proinflammatory and chemoattractant chemokine interleukin-8 (IL-8) inhibits cell proliferation induced by basic fibroblast growth factor (bFGF) in mouse endothelial cells isolated from subcutaneous sponge implant (sponge-induced mouse endothelial cells) and in bovine aortic endothelial GM 7373 cells. The mechanism of action of IL-8 was investigated in GM 7373 cells. IL-8 did not prevent the binding of bFGF to its tyrosine kinase FGF receptors (FGFRs) nor to cell surface heparan sulfate proteoglycans (HSPGs). A transient interaction of IL-8 with the cell before the addition of the growth factor was sufficient to prevent bFGF activity. The inhibitory activity of IL-8 was abolished by protein kinase C (PKC) inhibitors and was mimicked by the PKC activator 12-O-tetradecanoylphorbol-13-acetate. Accordingly, both IL-8 and 12-O-tetradecanoylphorbol-13-acetate caused a approximately 60% decrease of the binding capacity of GM 7373 cells due to the down-regulation of FGFRs. Several C-X-C and C-C chemokines exerted an inhibitory action on bFGF activity similar to IL-8. Soluble heparin, 6-O-desulfated heparin, N-desulfated heparin, and heparan sulfate but not 2-O-desulfated heparin, chondroitin-4-sulfate, hyaluronic acid, and K5 polysa...Continue Reading

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Citations

Jan 29, 2003·Biochemistry·Dingzhi WangAnn Richmond
Nov 5, 2003·The Journal of Experimental Medicine·Santos MañesCarlos Martínez-A
Aug 22, 2008·Immunological Investigations·Nicola F LintonChandrakant Tayade
Nov 26, 2004·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Mette M Rosenkilde, Thue W Schwartz
Apr 14, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paola ChiodelliMarco Rusnati

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