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Cell Immunol. 1996 Jul 10;171(1):95-101.

Prostaglandin E2 inhibits the nuclear transcription of the human interleukin 2, but not the Il-4, gene in human T cells by targeting transcription factors AP-1 and NF-AT.

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  • 1Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-1268, USA.

Abstract

Prostaglandin E2 (PGE2) release from activated macrophages and/or stimulation of T cells is associated with cAMP formation and activation of protein kinase A (PKA). cAMP inhibits Th1- but not Th2-cytokine production and may influence the nature of the immune response to a given antigen. Using DNA transfection and electrophoretic mobility shift assays (EMSA), we have examined the mechanisms for the transcriptional regulation of human IL-2 and IL-4 genes by PGE2. Stimulation of Jurkat cells with ionomycin and PMA in the presence of PGE2 inhibited the IL-2- but not the IL-4-promoter activity. In EMSAs, nuclear extracts from primary human T cells stimulated with ionomycin and phorbol esters in the presence of PGE2 demonstrated decreased binding at the AP-1 and NF-AT sites of the human IL-2 promoter; binding to the OCT-1 and NF-kappa B sites was not affected. These results suggest that cAMP regulates IL-2 production in human T cells by a transcriptional mechanism which involves discrete transactivating pathways for IL-2-promoter activation.

PMID:
8660843
[PubMed - indexed for MEDLINE]
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