PROSTAGLANDIN E(2) INHIBITS THE INTERLEUKIN-2 PROMOTER ACTIVITY THROUGH DOWN-REGULATION OF THE OCT-DEPENDENT TRANSCRIPTION OF THE OCTAMER MOTIF

Prostaglandins, mainly those of the E series (PGE), are modulators of immune responses. Indeed PGE(2) inhibits T cell activation and the tra nscription of the interleukin-2 (IL-2) gene, the major T cell growth f actor, We observed that PGE(2) inhibits IL-2 promoter transcription ac tivity by interfering with signals activating the (-96 to -66 bp) octa mer motif. This motif binds Oct-1 and Oct-2 as well as the phorbol est er and calcium ionophore-inducible jun and fos AP-1 factors. The PGE(2 )-dependent down-modulation is observed in the presence of either the endogenous transacting factor Oct-1 or the exogenously expressed Oct-2 . PGE(2) does not regulate octamer function by influencing the jun and fos mRNA or Oct-1 protein levels or their DNA-binding abilities. Func tional dissection of the octamer motif, through mutations of either th e AP-1 or the octamer sites, revealed that the AP-1 site is dispensabl e for PGE(2)-dependent inhibition which instead may occur through the interference with the Oct-mediated transactivation of the octamer elem ent, Our data suggest that the Oct-octamer interaction is a novel targ et of the PGE(2)-induced down-regulation of the IL-2 promoter, (C) 199 6 Academic Press, Inc.