|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
3
|
|
pubmed:dateCreated |
2000-12-12
|
|
pubmed:abstractText |
Using human blood monocytes (for determination of cyclooxygenase-2 (COX-2) mRNA by RT-PCR) and human whole blood (for prostanoid determination), the present study investigates the influence of the second messenger cAMP on lipopolysaccharide (LPS)-induced COX-2 expression with particular emphasis on the role of prostaglandin E(2) (PGE(2)) in this process. Elevation of intracellular cAMP with a cell-permeable cAMP analogue (dibutyryl cAMP), an adenylyl cyclase activator (cholera toxin), or a phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine) substantially enhanced LPS-induced PGE(2) formation and COX-2 mRNA expression, but did not modify COX-2 enzyme activity. Moreover, up-regulation of LPS-induced COX-2 expression was caused by PGE(2), butaprost (selective agonist of the adenylyl cyclase-coupled EP(2) receptor) and 11-deoxy PGE(1) (EP(2)/EP(4) agonist), whereas sulprostone (EP(3)/EP(1) agonist) left COX-2 expression unaltered. Abrogation of LPS-induced PGE(2) synthesis with the selective COX-2 inhibitor NS-398 caused a decrease in COX-2 mRNA levels that was restored by exogenous PGE(2) and mimicked by S(+)-flurbiprofen and ketoprofen. Overall, these results indicate a modulatory role of cAMP in the regulation of COX-2 expression. PGE(2), a cAMP-elevating final product of the COX-2 pathway, may autoregulate COX-2 expression in human monocytes via a positive feedback mechanism.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-3-isobutylxanthine,
http://linkedlifedata.com/resource/pubmed/chemical/Alprostadil,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Bucladesine,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Flurbiprofen,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-cyclohexyloxy-4-nitrophenyl)met...,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrobenzenes,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/butaprost
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Nov
|
|
pubmed:issn |
0006-291X
|
|
pubmed:author |
|
|
pubmed:copyrightInfo |
Copyright 2000 Academic Press.
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
30
|
|
pubmed:volume |
278
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
790-6
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:11095985-1-Methyl-3-isobutylxanthine,
pubmed-meshheading:11095985-Alprostadil,
pubmed-meshheading:11095985-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:11095985-Blood Platelets,
pubmed-meshheading:11095985-Bucladesine,
pubmed-meshheading:11095985-Cells, Cultured,
pubmed-meshheading:11095985-Cyclic AMP,
pubmed-meshheading:11095985-Cyclooxygenase 1,
pubmed-meshheading:11095985-Cyclooxygenase 2,
pubmed-meshheading:11095985-Dexamethasone,
pubmed-meshheading:11095985-Dinoprostone,
pubmed-meshheading:11095985-Flurbiprofen,
pubmed-meshheading:11095985-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:11095985-Humans,
pubmed-meshheading:11095985-Isoenzymes,
pubmed-meshheading:11095985-Lipopolysaccharides,
pubmed-meshheading:11095985-Membrane Proteins,
pubmed-meshheading:11095985-Monocytes,
pubmed-meshheading:11095985-Nitrobenzenes,
pubmed-meshheading:11095985-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:11095985-RNA, Messenger,
pubmed-meshheading:11095985-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11095985-Sulfonamides,
pubmed-meshheading:11095985-Transcription, Genetic
|
|
pubmed:year |
2000
|
|
pubmed:articleTitle |
Cyclooxygenase-2 expression in lipopolysaccharide-stimulated human monocytes is modulated by cyclic AMP, prostaglandin E(2), and nonsteroidal anti-inflammatory drugs.
|
|
pubmed:affiliation |
Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University Erlangen-Nürnberg, Fahrstrasse 17, Erlangen, D-91054, Germany. hinz@pharmakologie.uni-erlangen.de
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
