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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2001-4-18
pubmed:abstractText
Fever is triggered by an elevation of prostaglandin E(2) (PGE(2)) in the brain. However, the mechanism of its elevation remains unanswered. We herein cloned the rat glutathione-dependent microsomal prostaglandin E synthase (mPGES), the terminal enzyme for PGE(2) biosynthesis, and examined its induction in the rat brain after intraperitoneal injection of pyrogen lipopolysaccharide (LPS). In Northern blot analysis, mPGES mRNA was weakly expressed in the brain under the normal conditions but was markedly induced between 2 and 4 hr after the LPS injection. In situ hybridization study revealed that LPS-induced mPGES mRNA signals were mainly associated with brain blood vessels, especially vein or venular-type ones, in the whole brain area. Immunohistochemical study demonstrated that mPGES-like immunoreactivity was expressed in the perinuclear region of brain endothelial cells, which were identified as von Willebrand factor-positive cells. Furthermore, in the perinuclear region of the endothelial cells, mPGES was colocalized with cyclooxygenase-2 (COX-2), which is the enzyme essential for the production of the mPGES substrate PGH(2). Inhibition of cyclooxygenase-2 activity resulted in suppression of both PGE(2) level in the CSF and fever (Cao et al., 1997), suggesting that the two enzymes were functionally linked and that this link is essential for fever. These results demonstrate that brain endothelial cells play an essential role in the PGE(2) production during fever by expressing COX-2 and mPGES.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2669-77
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11306620-Animals, pubmed-meshheading:11306620-Base Sequence, pubmed-meshheading:11306620-Brain, pubmed-meshheading:11306620-Cerebrovascular Circulation, pubmed-meshheading:11306620-Cloning, Molecular, pubmed-meshheading:11306620-Cyclooxygenase 2, pubmed-meshheading:11306620-Dinoprostone, pubmed-meshheading:11306620-Disease Models, Animal, pubmed-meshheading:11306620-Endothelium, Vascular, pubmed-meshheading:11306620-Enzyme Inhibitors, pubmed-meshheading:11306620-Fever, pubmed-meshheading:11306620-Immunohistochemistry, pubmed-meshheading:11306620-In Situ Hybridization, pubmed-meshheading:11306620-Isoenzymes, pubmed-meshheading:11306620-Lipopolysaccharides, pubmed-meshheading:11306620-Male, pubmed-meshheading:11306620-Microsomes, pubmed-meshheading:11306620-Molecular Sequence Data, pubmed-meshheading:11306620-Organ Specificity, pubmed-meshheading:11306620-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:11306620-RNA, Messenger, pubmed-meshheading:11306620-Rats, pubmed-meshheading:11306620-Rats, Wistar, pubmed-meshheading:11306620-Sequence Homology, Amino Acid, pubmed-meshheading:11306620-Testis, pubmed-meshheading:11306620-von Willebrand Factor
pubmed:year
2001
pubmed:articleTitle
Coexpression of microsomal-type prostaglandin E synthase with cyclooxygenase-2 in brain endothelial cells of rats during endotoxin-induced fever.
pubmed:affiliation
Department of Neuropharmacology, Tokyo Metropolitan Institute for Neuroscience, Fuchu 183-8526, Japan. kyamagat@tmin.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't