Source:http://linkedlifedata.com/resource/pubmed/id/10640296
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2000-2-22
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pubmed:abstractText |
We 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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cannabinol,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
292
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
597-605
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10640296-Animals,
pubmed-meshheading:10640296-Cannabinol,
pubmed-meshheading:10640296-DNA Adducts,
pubmed-meshheading:10640296-DNA-Binding Proteins,
pubmed-meshheading:10640296-Dose-Response Relationship, Drug,
pubmed-meshheading:10640296-Electrophoresis,
pubmed-meshheading:10640296-Interleukin-2,
pubmed-meshheading:10640296-Mice,
pubmed-meshheading:10640296-Mice, Inbred C57BL,
pubmed-meshheading:10640296-NFATC Transcription Factors,
pubmed-meshheading:10640296-Nuclear Proteins,
pubmed-meshheading:10640296-Plasmids,
pubmed-meshheading:10640296-Thymoma,
pubmed-meshheading:10640296-Time Factors,
pubmed-meshheading:10640296-Transcription, Genetic,
pubmed-meshheading:10640296-Transcription Factor AP-1,
pubmed-meshheading:10640296-Transcription Factors,
pubmed-meshheading:10640296-Transfection,
pubmed-meshheading:10640296-Tumor Cells, Cultured
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pubmed:year |
2000
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pubmed:articleTitle |
Role 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.
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pubmed:affiliation |
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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