The stimulation of human synovial fibroblast plasminogen activator activity. Involvement of cyclic AMP and cyclooxygenase products.
The plasminogen activator activity of human synovial fibroblasts is raised by a monocyte-derived polypeptide, synovial activator and also by all-trans retinoic acid. The elevation of the synovial cell plasminogen activator activity by the two stimuli is potentiated both by agents which can raise cellular cyclic AMP levels, namely prostaglandin E2, cholera toxin and 3-isobutyl-1-methylxanthine, and also by exogenous 8-bromocyclic AMP. These findings suggest that there might be a substrate, which is phosphorylated by a cyclic AMP-dependent protein kinase and which is important in the modulation of the synovial cell plasminogen activator activity by the two stimuli. Prostanoids can be important in the stimulation of the synovial fibroblast plasminogen activator activity by mononuclear cell supernatants, since indomethacin can inhibit the increase in proteinase activity.
J A
JA
Hamilton
T
T
Leizer
S R
SR
Lingelbach
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D005439:Flufenamic Acid / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D010960:Plasminogen Activators / Q000032:analysis*; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000494:pharmacology; D013583:Synovial Membrane / Q000201:enzymology*; D014212:Tretinoin / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011458:Prostaglandins E; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014212:Tretinoin; D005439:Flufenamic Acid; D003907:Dexamethasone; D002772:Cholera Toxin; D000242:Cyclic AMP; D010960:Plasminogen Activators; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin