MODULATION OF PLASMINOGEN-ACTIVATOR AND PLASMINOGEN-ACTIVATOR INHIBITOR EXPRESSION IN THE HUMAN U373 GLIOBLASTOMA ASTROCYTOMA CELL-LINE BY INFLAMMATORY MEDIATORS

The human U373 glioblastoma/astrocytoma cell line was found to constitutively produce and secrete a plasminogen activator and a plasminogen activator inhibitor. The plasminogen activator was identified as urokinase based on apparent molecular weight, immunoblotting with anti-urokinase antibodies, and Northern blotting with a human urokinase cDNA probe. The inhibitor secreted by U373 cells was found to be related to the PAI-1 molecule based on reactivity with antihuman PAI-1 antibodies, apparent molecular weight, and Northern blot analysis with a human PAI-1 cDNA probe. The expression of both urokinase and the PAI-1-like molecule by U373 cells could be modulated by phorbol myristate acetate or by inflammatory mediators such as interferon-γ and interleukin-1. In the case of interleukin-1, the α form exhibited no detectable effect while the β form not only elevated inhibitor levels, it also appeared to induce the production of tissue plasminogen activator. Thus, in these cells interleukin-1β induces alterations in PA and PAI expression and interleukin-1α does not, even though the two forms are reported to utilize the same cellular receptor. © 1992.