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pubmed-article:10640296pubmed:abstractTextWe previously reported that immunosuppressive cannabinoids inhibited interleukin (IL)-2 steady-state mRNA expression and secretion by phorbol-12-myristate-13-acetate plus ionomycin-activated mouse splenocytes and EL4 murine T-cells. Here we show that inhibition of IL-2 production by cannabinol, a modest central nervous system-active cannabinoid, is mediated through the inhibition of IL-2 gene transcription. Moreover, electrophoretic mobility shift assays demonstrated that cannabinol markedly inhibited the DNA binding activity of nuclear factor of activated T-cells (NF-AT) and activator protein-1 (AP-1) in a time- and concentration-dependent manner in activated EL4 cells. The inhibitory effects produced by cannabinol on AP-1 DNA binding were quite transient, showing partial recovery by 240 min after cell activation and no effect on the activity of a reporter gene under the control of AP-1. Conversely, cannabinol-mediated inhibition of NF-AT was robust and sustained as demonstrated by an NF-AT-regulated reporter gene. Collectively, these results suggest that decreased IL-2 production by cannabinol in EL4 cells is due to the inhibition of transcriptional activation of the IL-2 gene and is mediated, at least in part, through a transient inhibition of AP-1 and a sustained inhibition of NF-AT.lld:pubmed
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pubmed-article:10640296pubmed:authorpubmed-author:RaoL GLGlld:pubmed
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pubmed-article:10640296pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:10640296pubmed:articleTitleRole of nuclear factor of activated T-cells and activator protein-1 in the inhibition of interleukin-2 gene transcription by cannabinol in EL4 T-cells.lld:pubmed
pubmed-article:10640296pubmed:affiliationDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon, Korea.lld:pubmed
pubmed-article:10640296pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:10640296pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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