Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
1999-9-1
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23085-93
pubmed:dateRevised
2008-11-21
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
pubmed:year
1999
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.
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.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't