EN
We report here that human astrocytoma cell line U373-MG is able to express genes of the following components of plasminogen activation system:PAI-1,PN-1,u-PA and t-PA. Treatment of these cells with IL-1 ß results in accumulation of PAI-1,PN-1 and u-PA mRNAs,whereas t-PA mRNA remains unaffected.IFN preferentially enhances PN-1 and PAI-1,EGF enhances PAI-1,u-PA and t-PA expression.Simultaneous addition of anti-inflammatory cytokines IL-4,IL-13 and IL-10 has little effect on the tested components,except induction of u-PA mRNA wich was further enhanced by IL-4.We have confirmed interesting time-dependent regulation of plasminogen activation system by EGF/IFN .Cells stimulated with EGF/IFN show at first increased proteolytic activity but after 24 h inhibition of proteolysis with PAI-1 would prevail.To understand the co- operative effect of EGF and IFN in PAI-1 induction the kinetics of activation of STAT1 was studied.It was found that although EGF alone does not activate STAT1,the STAT1 binding activity in the cells treated with the mixture of EGF/IFN was considerably prolonged.Our results indicate the importance of inflammatory cytokines and EGF in gene regulation of plasminogen activation system in astrocytoma cells.