Interferon-alpha 2 counteracts interleukin-1 alpha-stimulated expression of urokinase-type plasminogen activator in human foreskin microvascular endothelial cells in vitro.

We investigated the effect of interferon-alpha 2 (IFN-alpha 2) on interleukin-1 alpha (IL-1 alpha)-induced up-regulation of urokinase type plasminogen activator (u-PA) expression in human foreskin microvascular endothelial cells (HFMEC) and human umbilical vein endothelial cells (HUVEC) in vitro. When IFN-alpha 2 and IL-1 alpha were added to the cells simultaneously, IFN-alpha 2 inhibited IL-1 alpha-induced up-regulation of u-PA antigen in a dose- and time-dependent fashion in HFMEC, whereas in HUVEC no effect of IFN-alpha 2 on IL-1 alpha-induced u-PA was seen. IL-1 alpha-induced up-regulation of PAI-1 antigen in HFMEC was not counteracted by IFN-alpha 2. When IFN-alpha 2 was added to HFMEC 1 or 2 h after IL-1 alpha a significant inhibition in u-PA synthesis was seen, whereas when IFN-alpha 2 was added to the cells 8 h after IL-1 alpha no effect on the induction of u-PA synthesis by IL-1 alpha was seen. IFN-alpha 2 also inhibited significantly the IL-1 alpha stimulated up-regulation of specific u-PA mRNA expression. In conclusion, our data show that IFN-alpha 2 can counteract the IL-1 alpha-induced up-regulation of u-PA in a similar way as IFN-gamma. This effect, which seems to be specific for microvascular endothelial cells, could contribute to the modulation of endothelial cell-mediated extravascular proteolysis in processes such as wound healing, neovascularisation, and endothelial cell migration.