Linked Life Data

15659313

Source:http://linkedlifedata.com/resource/pubmed/id/15659313

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2005-1-20
pubmed:abstractText
We investigated the role of tumor necrosis factor-alpha (TNF-alpha) in the down-regulation of hepatic P-glycoprotein and cytochrome P450 (CYP) by endotoxin, using TNF-alpha gene-deficient (TNF-alpha-/-) mice. In the case of P-glycoprotein, endotoxin (10 mg/kg) significantly decreased the expression of hepatic P-glycoprotein in wild-type mice 6 h, but not 24 h, after intraperitoneal injection, with no significant differences in the constitutional expression of P-glycoprotein between wild-type mice and TNF-alpha-/- mice. However, endotoxin had no effect on the expression of P-glycoprotein in TNF-alpha-/- mice either 6 or 24 h after injection. When doxorubicin was administered intravenously to TNF-alpha-/- mice treated 6 h earlier with and without endotoxin, no significant differences in the plasma concentrations of doxorubicin 3 h after injection were observed between endotoxin-treated and untreated TNF-alpha-/- mice. These results suggest that TNF-alpha plays a pivotal role in the down-regulation of P-glycoprotein by endotoxin. In the case of CYP, the constitutive expression of hepatic CYP3A2 and CYP2C11 had a tendency to decline in TNF-alpha-/- mice compared with that in wild-type mice. Endotoxin significantly decreased the expression of hepatic CYP3A2 and CYP2C11 in wild-type mice 24 h after injection, and that decreased expression was significantly greater in TNF-alpha-/- mice than wild-type mice. When antipyrine was administered intravenously to wild-type mice and TNF-alpha-/- mice treated 24 h earlier with endotoxin, the plasma concentrations of antipyrine in TNF-alpha-/- mice 3 h after injection were significantly higher than those in wild-type mice. These findings suggest that TNF-alpha plays a key role in endotoxin-induced down-regulation of hepatic P-glycoprotein, as well as plays a protective role in the regulation of hepatic CYP3A2 and CYP2C11 against endotoxin-induced acute inflammatory response. In TNF-alpha-/- mice, other cytokines appear to function as compensation for the lack of endogenous TNF-alpha.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
507
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
229-37
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Role of tumor necrosis factor-alpha in down-regulation of hepatic cytochrome P450 and P-glycoprotein by endotoxin.
pubmed:affiliation
Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daikominami, Higashi-ku, Nagoya 461-867, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't