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Titolo:
Regulation of the hepatic multidrug resistance gene expression by endotoxin and inflammatory cytokines in mice
Autore:
Hartmann, G; Kim, H; Piquette-Miller, M;
Indirizzi:
Univ Toronto, Fac Pharm, Toronto, ON M5S 2S2, Canada Univ Toronto TorontoON Canada M5S 2S2 Pharm, Toronto, ON M5S 2S2, Canada
Titolo Testata:
INTERNATIONAL IMMUNOPHARMACOLOGY
fascicolo: 2, volume: 1, anno: 2001,
pagine: 189 - 199
SICI:
1567-5769(200102)1:2<189:ROTHMR>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
NECROSIS-FACTOR-ALPHA; SALT EXPORT PUMP; P-GLYCOPROTEIN; RAT-LIVER; MONOCLONAL-ANTIBODIES; CELL-LINES; INDUCED CHOLESTASIS; MOUSE; INTERLEUKIN-1; MDR1B;
Keywords:
inflammation; cytokines; P-glycoprotein; multidrug resistance; gene expression; liver;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Piquette-Miller, M Univ Toronto, Fac Pharm, 19 Russell St, Toronto, ON M5S2S2, Canada Univ Toronto 19 Russell St Toronto ON Canada M5S 2S2 da
Citazione:
G. Hartmann et al., "Regulation of the hepatic multidrug resistance gene expression by endotoxin and inflammatory cytokines in mice", INT IMMUNO, 1(2), 2001, pp. 189-199

Abstract

P-glycoprotein (PGP), an ATP-dependent membrane transporter is found in epithelial tissues of the liver, kidneys, intestine and blood-brain barrier. In tumor cells, PGP is often overexpressed and confers multidrug resistancetoward cancer chemotherapeutics. It has been previously shown in rats thatinduction of an inflammatory response evokes a decrease in hepatic expression of PGP. In order to identify the inflammatory mediators involved in this phenomenon, we examined the influence of experimentally induced inflammation and pro-inflammatory cytokines (interleukin (IL)-6. IL-1 beta and rumornecrosis factor (TNF)-alpha) on the hepatic expression of PGP in mice. A significant reduction in the hepatic expression of mdr1a, mdr1b, mdr2 and spgp genes were seen in endotoxin (lipopolysaccharide (LPS)) and turpentine-treated mice. Similarly, IL-6-treated mice displayed a 70% reduction in protein expression and a 40-70% reduction in the mRNA levels of all PGP mdr isoforms. Administration IL-1 beta caused an increase in both ndr1b mRNA and proteinexpression, however, mRNA levels of mdr1a, mdr2 and spgp were significantly reduced, Administration of TNF-Phi also caused increases in mdr1b mRNA. These findings indicate that IL-6 plays a principal role in the downregulation of PGP that is observed in the Livers of mice juring an inflammatory response. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/06/20 alle ore 02:03:16