PROSTAGLANDIN E(2) INDUCTION OF BINDING-ACTIVITY TO CRE AND AP-2 ELEMENTS IN HUMAN T-LYMPHOCYTES

Prostaglandins of the E series are immunomodulatory agents which exert inhibitory as well as stimulatory effects on a variety of immune resp onses. Since it is known that PGE(2) is able to increase cAMP levels, we investigated whether it can affect gene expression through the acti vation of the transcription factors which bind enhancer elements in th e promoter regions of cAMP-regulated genes. Using electrophoretic mobi lity shift assay, we demonstrated that a short treatment of human T ly mphocytes with PGE(2) induces specific binding activity to CRE and AP- 2, but not AP-1, DNA elements. Since the okadaic acid, a potent protei n phosphatase inhibitor, prolongs the induction of the binding activit y, phosphorylation events are likely to occur, This activity seems to be due to increased cAMP levels because forskolin and IBMX mimic the e ffects of PCE(2). More interestingly, transfection experiments with CR E-CAT plasmide show that PGE(2) activates the transcription of a CRE-c ontaining promoter. These data support the positive role for PGE(2) on some immune functions. (C) 1996 Academic Press, Inc.