Linked Life Data

21466820

Source:http://linkedlifedata.com/resource/pubmed/id/21466820

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-5-9
pubmed:abstractText
Interferon ? (IFN?) is used to treat malignancies and chronic viral infections. It has been found to decrease the rate of drug metabolism by acting on cytochrome P450 enzymes, but no studies have investigated the consequences of IFN? treatment on the CYP3A4 isoform, responsible for the metabolism of a majority of drugs. In this study, we have examined the effect of IFN? on CYP3A4 catalytic activity and expression in human hepatoma cells. We found that IFN? inhibits CYP3A4 activity and rapidly down-regulates the expression of CYP3A4, independent of de novo protein synthesis. Pharmacologic inhibitors and a dominant-negative mutant expression plasmid were used to dissect the molecular pathway required for CYP3A4 suppression, revealing roles for Jak1 and Stat1 and eliminating the involvement of the p38 mitogen-activated and extracellular regulated kinases. Treatment of hepatoma cells with IFN? did not affect the nuclear localization or relative abundance of Sp1 and Sp3 transcription factors, suggesting that the suppression of CYP3A4 by IFN? does not result from inhibitory Sp3 out-competing Sp1. To our knowledge, this is the first report that IFN? down-regulates CYP3A4 expression largely through the JAK-STAT pathway. Since IFN? suppresses CYP3A4 expression, caution is warranted when IFN? is administered in combination with CYP3A4 substrates to avoid the occurrence of adverse drug interactions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1096-0333
pubmed:author
pubmed:copyrightInfo
Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
253
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
130-6
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
The effect of interferon-? on the expression of cytochrome P450 3A4 in human hepatoma cells.
pubmed:affiliation
Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't