The Journal of Immunology, Vol 151, Issue 10 5154-5161, Copyright © 1993 by American Association of Immunologists

ARTICLES

Contrasting effects of transforming growth factor-beta and IL-1 on the regulation of plasminogen activator inhibitors in human synovial fibroblasts

JA Hamilton, J Wojta, M Gallichio, K McGrath and EL Filonzi
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia.

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.

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