| pubmed-article:15659313 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15659313 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:15659313 | lifeskim:mentions | umls-concept:C0242643 | lld:lifeskim |
| pubmed-article:15659313 | lifeskim:mentions | umls-concept:C0205054 | lld:lifeskim |
| pubmed-article:15659313 | lifeskim:mentions | umls-concept:C0010762 | lld:lifeskim |
| pubmed-article:15659313 | lifeskim:mentions | umls-concept:C0014264 | lld:lifeskim |
| pubmed-article:15659313 | lifeskim:mentions | umls-concept:C1456820 | lld:lifeskim |
| pubmed-article:15659313 | lifeskim:mentions | umls-concept:C0013081 | lld:lifeskim |
| pubmed-article:15659313 | pubmed:issue | 1-3 | lld:pubmed |
| pubmed-article:15659313 | pubmed:dateCreated | 2005-1-20 | lld:pubmed |
| pubmed-article:15659313 | 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. | lld:pubmed |
| pubmed-article:15659313 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15659313 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15659313 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15659313 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15659313 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15659313 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15659313 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15659313 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15659313 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:15659313 | pubmed:issn | 0014-2999 | lld:pubmed |
| pubmed-article:15659313 | pubmed:author | pubmed-author:NittaAtsumiA | lld:pubmed |
| pubmed-article:15659313 | pubmed:author | pubmed-author:NabeshimaTosh... | lld:pubmed |
| pubmed-article:15659313 | pubmed:author | pubmed-author:SaitoKuniakiK | lld:pubmed |
| pubmed-article:15659313 | pubmed:author | pubmed-author:TakagiKenjiK | lld:pubmed |
| pubmed-article:15659313 | pubmed:author | pubmed-author:HasegawaTakaa... | lld:pubmed |
| pubmed-article:15659313 | pubmed:author | pubmed-author:TakagiKenzoK | lld:pubmed |
| pubmed-article:15659313 | pubmed:author | pubmed-author:NadaiMasayuki... | lld:pubmed |
| pubmed-article:15659313 | pubmed:author | pubmed-author:ShimizuAkemiA | lld:pubmed |
| pubmed-article:15659313 | pubmed:author | pubmed-author:UeyamaJunJ | lld:pubmed |
| pubmed-article:15659313 | pubmed:author | pubmed-author:MiyoshiMikaM | lld:pubmed |
| pubmed-article:15659313 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15659313 | pubmed:day | 10 | lld:pubmed |
| pubmed-article:15659313 | pubmed:volume | 507 | lld:pubmed |
| pubmed-article:15659313 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15659313 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15659313 | pubmed:pagination | 229-37 | lld:pubmed |
| pubmed-article:15659313 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
| pubmed-article:15659313 | pubmed:meshHeading | pubmed-meshheading:15659313... | lld:pubmed |
| pubmed-article:15659313 | pubmed:meshHeading | pubmed-meshheading:15659313... | lld:pubmed |
| pubmed-article:15659313 | pubmed:meshHeading | pubmed-meshheading:15659313... | lld:pubmed |
| pubmed-article:15659313 | pubmed:meshHeading | pubmed-meshheading:15659313... | lld:pubmed |
| pubmed-article:15659313 | pubmed:meshHeading | pubmed-meshheading:15659313... | lld:pubmed |
| pubmed-article:15659313 | pubmed:meshHeading | pubmed-meshheading:15659313... | lld:pubmed |
| pubmed-article:15659313 | pubmed:meshHeading | pubmed-meshheading:15659313... | lld:pubmed |
| pubmed-article:15659313 | pubmed:meshHeading | pubmed-meshheading:15659313... | lld:pubmed |
| pubmed-article:15659313 | pubmed:meshHeading | pubmed-meshheading:15659313... | lld:pubmed |
| pubmed-article:15659313 | pubmed:meshHeading | pubmed-meshheading:15659313... | lld:pubmed |
| pubmed-article:15659313 | pubmed:meshHeading | pubmed-meshheading:15659313... | lld:pubmed |
| pubmed-article:15659313 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:15659313 | pubmed:articleTitle | Role of tumor necrosis factor-alpha in down-regulation of hepatic cytochrome P450 and P-glycoprotein by endotoxin. | lld:pubmed |
| pubmed-article:15659313 | pubmed:affiliation | Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daikominami, Higashi-ku, Nagoya 461-867, Japan. | lld:pubmed |
| pubmed-article:15659313 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15659313 | pubmed:publicationType | Comparative Study | lld:pubmed |
| pubmed-article:15659313 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15659313 | lld:pubmed |
