ALPHA-INTERFERON 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 (PA Is) was examined in human retinal pigment epithelial (RPE) cells in cu lture. Cultures of human RPE cells were incubated with either of the i nterferons for 48-96 h. The cell cultures were assayed using mRNA anal ysis and solid-phase immunocapture assay. Both interferons caused a ma rked decrease in PAI-1 mRNA expression after 48 h with no change in ur okinase-type plasminogen activator (u-PA) mRNA expression. A marked de crease 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-a lpha and IFN-gamma stimulate plasminogen-mediated pericellular proteol ysis of human RPE cells in culture by inhibiting PAI-1 gene expression .