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

Inflamm Res. 2001 Jul;50(7):362-70. doi: 10.1007/PL00000257.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
  • Animals
  • Blotting, Western
  • Cell Separation
  • Cells, Cultured
  • Coloring Agents
  • Dexamethasone / pharmacology
  • Gene Expression Regulation / drug effects
  • Genes, MDR / genetics
  • Glucocorticoids / pharmacology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Interleukin-1 / pharmacology*
  • Interleukin-6 / pharmacology*
  • RNA, Messenger / biosynthesis
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhodamine 123


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Coloring Agents
  • Glucocorticoids
  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Rhodamine 123
  • Dexamethasone