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Titolo:
NONCOMPETITIVE, CHEMOKINE-MEDIATED INHIBITION OF BASIC FIBROBLAST GROWTH FACTOR-INDUCED ENDOTHELIAL-CELL PROLIFERATION
Autore:
PRESTA M; BELLERI M; VECCHI A; HESSELGESSER J; MANTOVANI A; HORUK R;
Indirizzi:
UNIV BRESCIA,SCH MED,DEPT BIOMED SCI & BIOTECHNOL,UNIT GEN PATHOL & IMMUNOL,VIA VALSABBINA 19 I-25123 BRESCIA ITALY MARIO NEGRI INST PHARMACOL RES I-20157 MILAN ITALY BERLEX BIOSCI,DEPT IMMUNOL RICHMOND CA 94804
Titolo Testata:
The Journal of biological chemistry
fascicolo: 14, volume: 273, anno: 1998,
pagine: 7911 - 7919
SICI:
0021-9258(1998)273:14<7911:NCIOBF>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; PLASMINOGEN-ACTIVATOR PRODUCTION; HEPARAN-SULFATE PROTEOGLYCANS; FACTOR RECEPTOR; MITOGENIC ACTIVITY; PLATELET FACTOR-4; SIGNALING PATHWAY; DNA-SYNTHESIS; ANGIOGENESIS; BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
62
Recensione:
Indirizzi per estratti:
Citazione:
M. Presta et al., "NONCOMPETITIVE, CHEMOKINE-MEDIATED INHIBITION OF BASIC FIBROBLAST GROWTH FACTOR-INDUCED ENDOTHELIAL-CELL PROLIFERATION", The Journal of biological chemistry, 273(14), 1998, pp. 7911-7919

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 similar to 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 inhibi tory action on bFGF activity similar to IL-8, Soluble heparin, 6-O-desulfated heparin, N-desulfated heparin, and heparan sulfate but not a O-desulfated heparin, chondroitin-4-sulfate, hyaluronic acid, and K5 polysaccharide abrogated IL-8 inhibitory activity consistently with the presence of low affinity, high capacity HSPG-like chemokine-binding sites on GM 7373 cells, Finally, neovascularization induced by bFGF in murine subcutaneoussponge implants was reduced significantly by IL-8, In conclusion, IL-8 inhibits the mitogenic activity exerted by bFGF on cultured endothelial cells by a PKC-dependent, noncompetitive mechanism of action that causes FGFR down-regulation. This activity is shared by several chemokines and requires endothelial cell surface HSPGs. The endothelial cellline utilized in the present study may help to elucidate the complex interplay among chemokines, HSPGs, growth factors, and receptors in endothelial cells.

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Documento generato il 29/11/20 alle ore 00:17:26