Format

Send to

Choose Destination
See comment in PubMed Commons below
Inflamm Res. 2001 Jul;50(7):362-70.

Decreased expression of P-glycoprotein in interleukin-1beta and interleukin-6 treated rat hepatocytes.

Author information

1
Faculty of Pharmacy, University of Toronto, Ontario, Canada.

Abstract

OBJECTIVE AND DESIGN:

As acute inflammation is known to cause a reduction in hepatic P-Glycoprotein (PGP) expression and activity in rats, we tested the hypothesis that the pro-inflammatory cytokines interleukin (IL-)1beta and IL-6 also mediate reductions in PGP.

METHODS:

Hepatocytes were incubated with 0-50 ng/ml of cytokine for 24-72 h. PGP/mdr expression was examined by immunodetection and quantitative RT-PCR analysis and PGP efflux activity was assayed.

RESULTS:

PGP protein was significantly reduced in cells treated for 3 days with IL-1beta and 24 h with IL-6 (p < 0.05), maximal effects occurring at 5 ng/ml for each cytokine. PGP activity was reduced in both IL-1beta and IL-6 treated cells (p < 0.05). mdr1 mRNA was decreased in cells treated with IL-6, but not IL-1beta. spgp and mdr2 were not affected.

CONCLUSIONS:

Our data indicate that IL-6 and IL-1beta have suppressive effects on the expression and activity of PGP in cultured hepatocytes, likely occurring through distinct mechanisms. These cytokines may have a potential role in PGP regulation during inflammatory responses.

PMID:
11506391
DOI:
10.1007/PL00000257
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Springer
    Loading ...
    Support Center