Gamma-interferon counteracts interleukin-1 alpha stimulated expression of urokinase-type plasminogen activator in human endothelial cells in vitro.

The effect of gamma-interferon (gamma-IFN) on the interleukin-1 alpha (IL-1 alpha) induced stimulation of urokinase-type plasminogen activator (u-PA) expression in human foreskin microvascular endothelial cells (HFMEC) and in human umbilical vein endothelial cells (HUVEC) was investigated. When gamma-IFN and IL-1 alpha were added to the cells simultaneously, gamma-IFN inhibited the IL-1 alpha induced increase in u-PA antigen production in both HFMEC and HUVEC in a dose dependent fashion, with a maximum inhibitory effect achieved between 2.0 and 20.0 U/ml of gamma-IFN. Pretreatment of HFMEC with gamma-IFN for 1 hour before addition of IL-1 alpha resulted in a significant reduction in u-PA synthesis. However, when HFMEC were pretreated for 8 hours with gamma-IFN before the addition of IL-1 alpha the reduction in u-PA production was even more significant. When gamma-IFN was added to HFMEC 1 hour after IL-1 alpha, a significant inhibition in u-PA synthesis was seen. In contrast only a slight inhibition in IL-1 alpha induced u-PA production was seen when gamma-IFN was added to the cells 8 hours after IL-1 alpha. gamma-IFN also inhibited significantly the IL-1 alpha induced increase in u-PA specific mRNA in HUVEC and HFMEC.