Prostaglandin E2 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 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.
Felli
M P
MP
Department of Experimental Medicine, University of L'Aquila, Italy.
Moschella
C
C
Farina
A R
AR
Alesse
E
E
Screpanti
I
I
Teti
D
D
Frati
L
L
Gulino
A
A
D004268:DNA-Binding Proteins / Q000502:physiology; D015232:Dinoprostone / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D051863:Host Cell Factor C1; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D019169:Jurkat Cells; D050811:Octamer Transcription Factor-1; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000276:immunology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology*
D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D018398:Homeodomain Proteins; D051863:Host Cell Factor C1; D007376:Interleukin-2; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D015232:Dinoprostone