Source:http://linkedlifedata.com/resource/pubmed/id/10438477
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
33
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pubmed:dateCreated |
1999-9-1
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pubmed:abstractText |
Type II-secreted phospholipase A(2) (type II-sPLA(2)) is expressed in smooth muscle cells during atherosclerosis or in response to interleukin-1beta. The present study shows that the induction of type II-sPLA(2) gene by interleukin-1beta requires activation of the NFkappaB pathway and cytosolic PLA(2)/PPARgamma pathway, which are both necessary to achieve the transcriptional process. Interleukin-1beta induced type II-sPLA(2) gene dose- and time-dependently and increased the binding of NFkappaB to a specific site of type II-sPLA(2) promoter. This effect was abolished by proteinase inhibitors that block the proteasome machinery and NFkappaB nuclear translocation. Type II-sPLA(2) induction was also obtained by free arachidonic acid and was blocked by either AACOCF(3), a specific cytosolic-PLA(2) inhibitor, PD98059, a mitogen-activated protein kinase kinase inhibitor which prevents cytosolic PLA(2) activation, or nordihydroguaiaretic acid, a lipoxygenase inhibitor, but not by the cyclooxygenase inhibitor indomethacin, suggesting a role for a lipoxygenase product. Type II-sPLA(2) induction was obtained after treatment of the cells by 15-deoxy-Delta(12,14)-dehydroprostaglandin J(2), carbaprostacyclin, and 9-hydroxyoctadecadienoic acid, which are ligands of peroxisome proliferator-activated receptor (PPAR) gamma, whereas PPARalpha ligands were ineffective. Interleukin-1beta as well as PPARgamma-ligands stimulated the activity of a reporter gene containing PPARgamma-binding sites in its promoter. Binding of both NFkappaB and PPARgamma to their promoter is required to stimulate the transcriptional process since inhibitors of each class block interleukin-1beta-induced type II-sPLA(2) gene activation. We therefore suggest that NFkappaB and PPARgamma cooperate at the enhanceosome-coactivator level to turn on transcription of the proinflammatory type II-sPLA(2) gene.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingomyelin Phosphodiesterase,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
23085-93
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10438477-Animals,
pubmed-meshheading:10438477-Base Sequence,
pubmed-meshheading:10438477-Biological Transport,
pubmed-meshheading:10438477-Cells, Cultured,
pubmed-meshheading:10438477-Ceramides,
pubmed-meshheading:10438477-Cycloheximide,
pubmed-meshheading:10438477-DNA Primers,
pubmed-meshheading:10438477-Dactinomycin,
pubmed-meshheading:10438477-Dose-Response Relationship, Drug,
pubmed-meshheading:10438477-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:10438477-Interleukin-1,
pubmed-meshheading:10438477-Male,
pubmed-meshheading:10438477-Muscle, Smooth, Vascular,
pubmed-meshheading:10438477-NF-kappa B,
pubmed-meshheading:10438477-Phospholipases A,
pubmed-meshheading:10438477-RNA, Messenger,
pubmed-meshheading:10438477-Rats,
pubmed-meshheading:10438477-Rats, Wistar,
pubmed-meshheading:10438477-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:10438477-Sphingomyelin Phosphodiesterase,
pubmed-meshheading:10438477-Transcription Factors,
pubmed-meshheading:10438477-Transcriptional Activation
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pubmed:year |
1999
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pubmed:articleTitle |
Interleukin 1beta induces type II-secreted phospholipase A(2) gene in vascular smooth muscle cells by a nuclear factor kappaB and peroxisome proliferator-activated receptor-mediated process.
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pubmed:affiliation |
Unité Propre de Recherche de l'Université Pierre et Marie Curie, Associée au CNRS, ESA7079, 7 quai St. Bernard, 75252 Paris, Cedex 5, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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