Human synovial fibroblast plasminogen activator. Modulation of enzyme activity by antiinflammatory steroids.
Human synovial fibroblasts in culture have been shown to have low plasminogen activator (PA) activity; however, conditioned medium from concanavalin A-stimulated peripheral blood mononuclear cells (c-MCCM) stimulates the cellular levels of this protease. The present study shows that low concentrations of a series of antiinflammatory steroids inhibit the PA activities of both unstimulated and c-MCCM-stimulated fibroblasts. Dexamethasone, the corticosteroid studied in greatest detail, suppresses both the extracellular and cell-associated enzyme activities; this inhibition is rapid, reversible, and is not due to the inhibition of cellular RNA, protein, or DNA synthesis. PA has been invoked as possibly being generally important for the processes of cell migration, tissue remodeling, and inflammation. These in vitro observations suggest that physiologic and/or pharmacologic control of the PA levels in synovial fibroblasts might also be achieved in vivo by the interacting effects of mutually antagonistic agents, namely, a product from stimulated mononuclear cells and glucocorticoids.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects; D005347:Fibroblasts / Q000201:enzymology / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D010960:Plasminogen Activators / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D003470:Culture Media; D005938:Glucocorticoids; D003907:Dexamethasone; D010960:Plasminogen Activators