Linked Life Data

17317725

Source:http://linkedlifedata.com/resource/pubmed/id/17317725

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2007-5-31
pubmed:abstractText
Macrophage cyclooxygenase-2 (COX-2) plays an important role in prostaglandin E2 and thromboxane A2 production. Statins are inhibitors of HMG CoA (3-Hydroxy-3-methylglutaryl coenzyme A) reductases and cholesterol synthesis, which block the expression of several inflammatory proteins independent of their capacity to lower endogenous cholesterol. In the present study, we investigated the effect of simvastatin and mevastatin on COX-2 induction in human monocytic cell line U937 and analyzed the underlying mechanisms. Pretreatment of U937 cells with simvastatin or mevastatin for 24 h resulted in a significant reduction in the lipopolysaccharide (LPS)-dependent induction of prostaglandin E2, thromboxane A2 synthesis, and COX-2 expression. Mevalonate, the direct metabolite of HMG CoA reductase, and farnesyl pyrophosphate and geranylgeranyl-pyrophosphate, intermediates of the mevalonate pathway, significantly reversed the inhibitory effect of statins on COX-2. An inhibitor of geranylgeranyl transferases, GGTI-286 mimicked the effect of statins on COX-2 expression. Cytonecrotic factor-1 increased LPS-dependent expression of COX-2. Treatment of cells with NSC 23766, an inhibitor of Rac, which we demonstrated to block Rac 2 activation, resulted in an inhibition of the LPS-dependent expression of COX-2. Whereas no effect was obtained with RhoA/C blocker, C3 exoenzyme. Gel retardation experiments and NFkappaB-p65 transcription factor assay showed that simvastatin and NSC 23766 decrease significantly NF-kappaB complex formation. In macrophages, the antiinflammatory effects of statins are mediated in part through the inhibition of COX-2 and prostanoids. Rac GTPase protein is identified as one of the targets of statins in this regulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl-CoA..., http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Lovastatin, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Mevalonic Acid, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Simvastatin, http://linkedlifedata.com/resource/pubmed/chemical/compactin, http://linkedlifedata.com/resource/pubmed/chemical/rac GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/rac2 GTP-binding protein
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1665-74
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Modulation of COX-2 expression by statins in human monocytic cells.
pubmed:affiliation
Department of Biochemistry, American University of Beirut, P.O. Box 11-236 Beirut, Lebanon. ah31@aub.edu.lb
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't