Linked Life Data

15860574

Source:http://linkedlifedata.com/resource/pubmed/id/15860574

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-7-18
pubmed:abstractText
Inflammatory agents such as lipopolysaccharide (LPS) down-regulate the hepatic expression of many cytochrome P450 (P450) mRNAs and proteins. Previous studies suggested that suppression of some P450 mRNAs could involve the regulation or modulation of the nuclear receptors peroxisome proliferator-activated receptor alpha (PPARalpha) or pregnane X receptor (PXR). To determine the involvement of these receptors in P450 down-regulation, PPARalpha knockout (KO), PXR KO, and appropriate wild-type (WT) mice were administered either saline or 1 mg/kg LPS. Hepatic mRNA and protein expression of several P450 isoforms, interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF) alpha, alpha1-acid glycoprotein (AGP), and fibrinogen (FBG) were examined 16 h later. LPS administration significantly decreased the hepatic expression of CYP1A2, 2A5, 2C29, 2E1, 3A11, 4A10, and 4A14 mRNAs in both groups of PPARalpha and PXR mice, whereas CYP3A13 mRNA was increased slightly in PPARalpha WT and KO mice, but not in PXR mice. Effects of LPS administration on mouse hepatic P450 proteins (probed using rat P450 2C, 3A, 4A, and 2E antibodies) were consistent with mRNA results in most cases. LPS treatment significantly increased IL-1beta, IL-6, TNFalpha, AGP, and FBG mRNA in both PPARalpha and PXR mice, with the greatest effect observed with TNFalpha. Because decreases in P450 mRNA expression were essentially identical in both WT and KO mice for both nuclear receptors, these data indicate that down-regulation of P450 during inflammation does not require the nuclear receptors PPARalpha and PXR.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
314
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
703-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15860574-Acute-Phase Proteins, pubmed-meshheading:15860574-Animals, pubmed-meshheading:15860574-Blotting, Western, pubmed-meshheading:15860574-Cytochrome P-450 Enzyme System, pubmed-meshheading:15860574-Cytokines, pubmed-meshheading:15860574-DNA, Complementary, pubmed-meshheading:15860574-Down-Regulation, pubmed-meshheading:15860574-Endotoxins, pubmed-meshheading:15860574-Female, pubmed-meshheading:15860574-Gene Expression Regulation, Enzymologic, pubmed-meshheading:15860574-Inflammation, pubmed-meshheading:15860574-Lipopolysaccharides, pubmed-meshheading:15860574-Liver, pubmed-meshheading:15860574-Mice, pubmed-meshheading:15860574-Mice, Knockout, pubmed-meshheading:15860574-Microsomes, Liver, pubmed-meshheading:15860574-PPAR alpha, pubmed-meshheading:15860574-RNA, pubmed-meshheading:15860574-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:15860574-Receptors, Steroid, pubmed-meshheading:15860574-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2005
pubmed:articleTitle
Hepatic cytochrome P450 gene regulation during endotoxin-induced inflammation in nuclear receptor knockout mice.
pubmed:affiliation
Department of Pharmacology, Emory University School of Medicine, 5119 O. Wayne Rollins Research Center, 1510 Clifton Road NE, Atlanta, GA 30322, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural