Prostaglandin E2Inhibits 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 PGE2inhibits T cell activation and the transcription of the interleukin-2 (IL-2) gene, the major T cell growth factor. We observed that PGE2inhibits IL-2 promoter transcription activity by interfering with signals activating the (−96 to −66 bp) octamer motif. This motif binds Oct-1 and Oct-2 as well as the phorbol ester and calcium ionophore-induciblejunandfosAP-1 factors. The PGE2-dependent down-modulation is observed in the presence of either the endogenous transacting factor Oct-1 or the exogenously expressed Oct-2. PGE2does not regulate octamer function by influencing thejunandfosmRNA or Oct-1 protein levels or their DNA-binding abilities. Functional dissection of the octamer motif, through mutations of either the AP-1 or the octamer sites, revealed that the AP-1 site is dispensable for PGE2-dependent inhibition which instead may occur through the interference with the Oct-mediated transactivation of the octamer element. Our data suggest that the Oct–octamer interaction is a novel target of the PGE2-induced down-regulation of the IL-2 promoter.