Prostaglandin E2 induction of binding activity to CRE and AP-2 elements in human T lymphocytes.
Prostaglandins of the E series are immunomodulatory agents which exert inhibitory as well as stimulatory effects on a variety of immune responses. Since it is known that PGE2 is able to increase cAMP levels, we investigated whether it can affect gene expression through the activation of the transcription factors which bind enhancer elements in the promoter regions of cAMP-regulated genes. Using electrophoretic mobility shift assay, we demonstrated that a short treatment of human T lymphocytes with PGE2 induces specific binding activity to CRE and AP-2, but not AP-1, DNA elements. Since the okadaic acid, a potent protein phosphatase inhibitor, prolongs the induction of the binding activity, phosphorylation events are likely to occur. This activity seems to be due to increased cAMP levels because forskolin and IBMX mimic the effects of PGE2. More interestingly, transfection experiments with CRE-CAT plasmide show that PGE2 activates the transcription of a CRE-containing promoter. These data support the positive role for PGE2 on some immune functions.
Micali
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Istituto di Patologia Generale, Universita degli Studi di Messina, Italy.
Medici
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N
Sottile
A
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Venza
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M
Venza
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I
Nigro
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V
Puca
G A
GA
Teti
D
D
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001665:Binding Sites; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D005576:Colforsin; D019319:Okadaic Acid; D004247:DNA; D000242:Cyclic AMP; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine