Suppression of urokinase-type plasminogen activator mRNA levels in human fibrosarcoma cells and synovial fibroblasts by anti-inflammatory glucocorticoids.

Abstract

Suppression of plasminogen activator (PA) activity has been invoked as being part of the general anti-inflammatory action of glucocorticoids. Low concentrations of the synthetic glucocorticoid, dexamethasone (Dex), reduce urokinase-type PA mRNA levels in two cell types, namely a human fibrosarcoma line, HT1080, and synovial fibroblast-like cells isolated from human joints. Conversely, metallothionein IIa (MTIIa) mRNA levels in these cells are raised by Dex. These findings, by suggesting that it is possible to suppress urokinase-type PA activity at the level of gene expression, may have therapeutic implications for diseases such as rheumatoid arthritis where proteases may be contributing to the extensive tissue damage and inflammation.