Regulation of the secretion of urokinase-type plasminogen activator and type-1 plasminogen activator inhibitor in T98G human glioblastoma cells by cytokines and dexamethasone

Abstract

The plasminogen-plasmin system plays an important role in regulating tumor invasion, tissue remodelling, and neovascularization. We investigated the effect of various cytokines on fibrinolytic activity produced by T98G glioblastoma cells. The cytokines used were interleukin (IL)-1α, and β, IL-2, IL-3, IL-4, IL-6, and tumor necrosis factor (TNF) α and β. The highest fibrinolytic activity measured by fibrin autography was observed in the conditioned medium of T98G cells treated by IL-1α and TNFα. IL-4 and IL-6 produced a slight increase in fibrinolytic activity, while IL-2 and IL-3 had little effect. Dexamethasone significantly decreased the fibrinolytic activity. Zymographic analysis, ELISA, and Northern blot analysis showed that the increased fibrinolytic activity induced by IL-1 and TNF was caused by increased urokinase-type plasminogen activator (uPA) secretion, and that decreased activity induced by dexamethasone was caused by a decrease in uPA and an increase in type-1 plasminogen activator inhibitor (PAI-1) secretion. These findings suggest that inflammatory mediators are involved in the regulation of brain tumor invasiveness and neovascularization.