Alpha- and gamma-interferon inhibit plasminogen activator inhibitor-1 gene expression in human retinal pigment epithelial cells.

The effect of interferons IFN-alpha and IFN-gamma on the production of plasminogen activators (PAs) and plasminogen activator inhibitors (PAIs) was examined in human retinal pigment epithelial (RPE) cells in culture. Cultures of human RPE cells were incubated with either of the interferons for 48-96 h. The cell cultures were assayed using mRNA analysis and solid-phase immunocapture assay. Both interferons caused a marked decrease in PAI-1 mRNA expression after 48 h with no change in urokinase-type plasminogen activator (u-PA) mRNA expression. A marked decrease in PAI-1 activity and concomitant increase in u-PA activity in the culture medium appeared only after 72-96 h. We conclude that IFN-alpha and IFN-gamma stimulate plasminogen-mediated pericellular proteolysis of human RPE cells in culture by inhibiting PAI-1 gene expression.