Tissue plasminogen activator-induced secretion of type-1 plasminogen activator inhibitor in cultured human fibroblasts.
Tissue plasminogen activator (t-PA) regulation of type-1 plasminogen activator inhibitor (PAI-1) secretion by WI-38 human fibroblasts was investigated utilizing a specific ELISA to measure PAI-1 antigen levels. Incubation of confluent fibroblasts with t-PA in serum-free medium resulted in a concentration and time-dependent increase in the secretion of PAI-1, with the maximum response (a two-fold increase) observed following a 4 hour incubation with 0.1 microM t-PA. This t-PA effect was reduced by cycloheximide, suggesting that the involvement of specific protein synthesis, and by inhibitors of t-PA's enzymatic activity, suggesting a requirement for a free catalytic site. The t-PA effect could not be attributed to endotoxin contamination. Increased levels in cell-associated PAI-1 were also detected following incubation of fibroblasts with t-PA. This previously undescribed effect, although seen at relatively high concentrations of t-PA, may have important biological implications.
Reilly
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E.I. du Pont de Nemours and Company, Medical Products Department, Wilmington, DE 19880-0400.
Greenplate
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Timmermans
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D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010960:Plasminogen Activators / Q000494:pharmacology; D015849:Plasminogen Inactivators / Q000378:metabolism*; D013268:Stimulation, Chemical; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D008070:Lipopolysaccharides; D015849:Plasminogen Inactivators; D003513:Cycloheximide; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator