Source:http://linkedlifedata.com/resource/pubmed/id/10999939
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2000-10-16
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pubmed:abstractText |
The prostaglandin synthase cyclooxygenase-2 (COX-2) is produced by an immediate early response gene induced in most cells by a variety of stimuli. Several studies have shown that the immunosuppressant cyclosporin (CsA) interferes with prostanoid metabolism, but the mechanisms are unclear. Here we examine the effect of CsA on COX-2 mRNA induction in cultured rat vascular smooth muscle cells (VSMC) that natively express the nuclear factor of activated T-cells, a known mediator of CsA-sensitive transcription. CsA significantly suppresses strong COX-2 mRNA induction caused by the Ca(2+)-mobilizing mitogens UTP, angiotensin II, and platelet-derived growth factor-BB, and the synergistic induction caused by costimulation with ionomycin and a phorbol ester. Forskolin and interleukin-1beta are substantially weaker COX-2 mRNA inducers, and CsA does not inhibit their effect. CsA strongly inhibits UTP-, angiotensin II-, and platelet-derived growth factor-BB-stimulated COX-2 gene transcription as measured by nuclear run-on or promoter-reporter studies, but has no effect on mRNA induction caused by post-transcriptional stabilization of a distal COX-2 mRNA 3'-untranslated region regulatory element. These data show that CsA selectively inhibits mitogen-induced COX-2 gene expression by a transcriptional mechanism that may involve the nuclear factor of activated T-cells.
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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/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogens,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
58
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
701-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10999939-Animals,
pubmed-meshheading:10999939-Cells, Cultured,
pubmed-meshheading:10999939-Cyclooxygenase 2,
pubmed-meshheading:10999939-Cyclosporine,
pubmed-meshheading:10999939-Drug Interactions,
pubmed-meshheading:10999939-Enzyme Inhibitors,
pubmed-meshheading:10999939-Isoenzymes,
pubmed-meshheading:10999939-Mitogens,
pubmed-meshheading:10999939-Muscle, Smooth, Vascular,
pubmed-meshheading:10999939-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:10999939-RNA, Messenger,
pubmed-meshheading:10999939-Rats,
pubmed-meshheading:10999939-Transcription, Genetic
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pubmed:year |
2000
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pubmed:articleTitle |
Cyclosporin A selectively inhibits mitogen-induced cyclooxygenase-2 gene transcription in vascular smooth muscle cells.
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pubmed:affiliation |
Department of Pharmacology, Emory University School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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