Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-5-4
pubmed:abstractText
The P-glycoprotein (Pgp), a drug efflux pump, is expressed in intestinal epithelial cells, where it constitutes a barrier against xenobiotics. In inflammatory bowel disease, a dysregulation in the production of tumor necrosis factor (TNF)alpha and interferon (IFN)gamma, and an alteration of Pgp expression and activity have been reported. The aim of this study was to investigate the effects of TNF alpha and IFN gamma on intestinal Pgp expression, activity, and localization in Caco-2 cells grown on filters. TNF alpha induced both a strong time-dependent diminution (-56%) of MDR1 mRNA (semiquantitative reverse transcription polymerase chain reaction) and a significant decrease of unidirectional transport of rhodamine 123 after 48 h of exposure at 10 ng/mL. By confocal laser scanning microscopy, the Pgp was mainly localized to the apical plasma membrane of both control and TNF alpha-treated cells. By contrast, IFN gamma induced up-regulation of both mRNA MDR1 and Pgp protein expression without incidence on Pgp activity. Interestingly, a colocalization of Pgp with lateral F-actin was observed. Associated with TNF alpha, IFN gamma produced neither an antagonist nor synergistic effect on Pgp activity. In conclusion, our results demonstrate an inhibitory effect of TNF alpha and no effect of IFN gamma on Pgp transport activity using rhodamine 123 as a substrate. Mechanisms of action of these cytokines remain to be studied.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-3549
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1524-1536, 2004
pubmed:issnType
Print
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1524-36
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Effect of tumor necrosis factor-alpha and interferon-gamma on intestinal P-glycoprotein expression, activity, and localization in Caco-2 cells.
pubmed:affiliation
Laboratoire de Physiologie-Pharmacie Clinique, UPRES 2706, Faculté de Pharmacie, 5 rue J-B Clément, 92296 Châtenay-Malabry Cedex, France.
pubmed:publicationType
Journal Article, Comparative Study