Chloroquine's modulation of endothelial cell activity induced with basic fibroblast growth factor and human serum: effect on mitogenesis, protease production and cell migration.
Chloroquine modulates the activity of cultured human microvascular endothelial (HOME) cells in a complex fashion. At concentrations of 5-25 microM, CQ inhibits basic fibroblast growth factor (bFGF-) and human serum-induced mitogenic activity in these cells, in a dose-dependent manner. The kinetics of CQ's inhibitory actions on serum-induced mitogenesis in HOME cells slowly develops with only 30% of maximum inhibition reached after 24 hours. In HOME cells grown in serum-free medium, CQ raised tissue-plasminogen activator antigen levels in cell extracts. There was also a potentiation of bFGF-induced t-PA production. The kinetics of CQ's stimulatory effect on t-PA production by HOME cells, suggest that this effect precedes its inhibitory actions on mitogenesis. This effect of CQ on t-PA generation in endothelial cells was susceptible to cycloheximide inhibition. In wound assays, HOME cell migration, induced with bFGF and HS, was potentiated by CQ.
Inyang
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INSERM U 150, Hopital Lariboisiere, Paris, France.
Bikfalvi
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Lu
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Tobelem
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D001798:Blood Proteins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D010450:Endopeptidases / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006801:Humans; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D001798:Blood Proteins; D005346:Fibroblast Growth Factors; D002738:Chloroquine; D010450:Endopeptidases; D010959:Tissue Plasminogen Activator