Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-2-22
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
292
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
597-605
pubmed:dateRevised
2007-11-14
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
pubmed:year
2000
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.
pubmed:affiliation
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon, Korea.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.