Contrasting effects of transforming growth factor-beta and IL-1 on the regulation of plasminogen activator inhibitors in human synovial fibroblasts.
TGF-beta increased in a dose-dependent manner the production of plasminogen activator inhibitor-1 (PAI-1) in cultured human synovial fibroblast-like cells, as measured by ELISA. Significant increases in PAI-1 were first detected in cell supernatants within 4 h after cytokine addition. Increases were also observed in PAI-1 mRNA expression. IL-1 suppressed these increases in PAI-1 Ag and mRNA. In contrast, when PAI-2 levels were measured by ELISA, TGF-beta did not raise them but inhibited slightly the enhancement caused by IL-1 of PAI-2 Ag and mRNA. Therefore TGF-beta selectively stimulates the formation of one PAI; TGF-beta and IL-1 have opposing effects on PAI-1 and PAI-2 synthesis in the synovial cells. These findings are proposed to help define the control of fibrinolysis and tissue remodeling in the rheumatoid synovium.
Hamilton
J A
JA
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia.
Wojta
J
J
Gallichio
M
M
McGrath
K
K
Filonzi
E L
EL
D002478:Cells, Cultured; D005347:Fibroblasts; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D017396:Plasminogen Activator Inhibitor 2 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007375:Interleukin-1; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta