Source:http://linkedlifedata.com/resource/pubmed/id/12376404
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2002-10-11
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pubmed:abstractText |
The febrile response to lipopolysaccharide (LPS) consists of three phases (phases I-III), all requiring de novo synthesis of prostaglandin (PG) E(2). The major mechanism for activation of PGE(2)-synthesizing enzymes is transcriptional upregulation. The triphasic febrile response of Wistar-Kyoto rats to intravenous LPS (50 microg/kg) was studied. Using real-time RT-PCR, the expression of seven PGE(2)-synthesizing enzymes in the LPS-processing organs (liver and lungs) and the brain "febrigenic center" (hypothalamus) was quantified. Phase I involved transcriptional upregulation of the functionally coupled cyclooxygenase (COX)-2 and microsomal (m) PGE synthase (PGES) in the liver and lungs. Phase II entailed robust upregulation of all enzymes of the major inflammatory pathway, i.e., secretory (s) phospholipase (PL) A(2)-IIA --> COX-2 --> mPGES, in both the periphery and brain. Phase III was accompanied by the induction of cytosolic (c) PLA(2)-alpha in the hypothalamus, further upregulation of sPLA(2)-IIA and mPGES in the hypothalamus and liver, and a decrease in the expression of COX-1 and COX-2 in all tissues studied. Neither sPLA(2)-V nor cPGES was induced by LPS. The high magnitude of upregulation of mPGES and sPLA(2)-IIA (1,257-fold and 133-fold, respectively) makes these enzymes attractive targets for anti-inflammatory therapy.
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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/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
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 |
Nov
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pubmed:issn |
0363-6119
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
283
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
R1104-17
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12376404-Animals,
pubmed-meshheading:12376404-Dinoprostone,
pubmed-meshheading:12376404-Fever,
pubmed-meshheading:12376404-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:12376404-Hypothalamus,
pubmed-meshheading:12376404-Lipopolysaccharides,
pubmed-meshheading:12376404-Liver,
pubmed-meshheading:12376404-Male,
pubmed-meshheading:12376404-Phospholipases A,
pubmed-meshheading:12376404-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:12376404-RNA, Messenger,
pubmed-meshheading:12376404-Rats,
pubmed-meshheading:12376404-Rats, Inbred WKY,
pubmed-meshheading:12376404-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12376404-Transcription, Genetic,
pubmed-meshheading:12376404-Up-Regulation
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pubmed:year |
2002
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pubmed:articleTitle |
Prostaglandin E(2)-synthesizing enzymes in fever: differential transcriptional regulation.
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pubmed:affiliation |
Trauma Research, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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