Opposing effects of interleukin-1 and transforming growth factor-beta on the regulation of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 expression by human mesangial cells.

Several proteases have been implicated in regulating the turnover of mesangial matrix within the glomerulus. One such group, the plasminogen activators (PAs) and their inhibitor, PA inhibitor type-1 (PAI-1), is produced by glomerular cells with altered expression during nephritis. We report the effect of IL-1 and transforming growth factor-beta (TGF-beta) and a combination of the two cytokines on the secretion of tissue-type PA (t-PA) and PAI-1 from human mesangial cells. IL-1 significantly downregulates PAI-1 production and upregulates t-PA over a range of concentrations (1-10 U/ml), while TGF-beta (0.5-10 ng/ml) has the opposite effect. The combined effect of these factors is that TGF-beta attenuates the increase in t-PA and decrease in PAI-1 expression caused by IL-1, and has a dominant effect upon their secretion, thus decreasing t-PA and increasing PAI-1. These findings contribute to our understanding of fibrinolysis and tissue remodelling within the glomerular mesangium during the course of nephritis.