151. Prostaglandin E2 inhibits the interleukin-2 promoter activity through down-regulation of the Oct-dependent transcription of the octamer motif.
- Author
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Felli MP, Moschella C, Farina AR, Alesse E, Screpanti I, Teti D, Frati L, and Gulino A
- Subjects
- DNA-Binding Proteins physiology, Down-Regulation drug effects, Down-Regulation immunology, Homeodomain Proteins biosynthesis, Host Cell Factor C1, Humans, Interleukin-2 antagonists & inhibitors, Jurkat Cells, Octamer Transcription Factor-1, Promoter Regions, Genetic drug effects, Proto-Oncogene Proteins c-fos biosynthesis, Proto-Oncogene Proteins c-jun biosynthesis, Transcription Factor AP-1 biosynthesis, Transcription Factors biosynthesis, Transcription, Genetic drug effects, Dinoprostone physiology, Down-Regulation genetics, Homeodomain Proteins genetics, Interleukin-2 genetics, Promoter Regions, Genetic immunology, Transcription Factors genetics, Transcription, Genetic immunology
- Abstract
Prostaglandins, mainly those of the E series (PGE), are modulators of immune responses. Indeed PGE2 inhibits T cell activation and the transcription of the interleukin-2 (IL-2) gene, the major T cell growth factor. We observed that PGE2 inhibits 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-inducible jun and fos AP-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. PGE2 does not regulate octamer function by influencing the jun and fos mRNA 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.
- Published
- 1996
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