Inflammation Research

, Volume 50, Issue 7, pp 362–370

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

  • M. Sukhai
  • A. Yong
  • A. Pak
  • M. Piquette-Miller

DOI: 10.1007/PL00000257

Cite this article as:
Sukhai, M., Yong, A., Pak, A. et al. Inflamm. res. (2001) 50: 362. doi:10.1007/PL00000257

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-)1β 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-1β 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-1β and IL-6 treated cells (p < 0.05). mdr1 mRNA was decreased in cells treated with IL-6, but not IL-1β. spgp and mdr2 were not affected.¶Conclusions: Our data indicate that IL-6 and IL-1β 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.

Key words: Cytokines - Multidrug Resistance - P-Glycoprotein - Gene Regulation - Hepatocytes 

Copyright information

© Birkhäuser Verlag, 2001

Authors and Affiliations

  • M. Sukhai
    • 1
  • A. Yong
    • 1
  • A. Pak
    • 1
  • M. Piquette-Miller
    • 1
  1. 1.Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Ontario, Canada, M5S 2S2. Fax: 416-978-8511, e-mail: m.piquette.miller@utoronto.ca.CA