The interleukin-2 receptor down-regulates the expression of cytochrome P450 in cultured rat hepatocytes

Gastroenterology. 1995 Nov;109(5):1589-99. doi: 10.1016/0016-5085(95)90648-7.


Background & aims: Interleukin (IL) 2 is used in advanced cancers, but its effects on cytochrome P450 remain unknown. Other cytokines down-regulate hepatic cytochrome P450, but it is not known whether this involves cytokine receptors. The aim of this study was to determine whether the IL-2 receptor is expressed on hepatocytes and whether its activation by IL-2 depresses cytochrome P450 in cultured rat hepatocytes.

Methods: A monoclonal antibody specific for the rat IL-2 receptor alpha chain was used to label the receptor, whereas effects on cytochrome P450 were determined after 24 hours of culture with human recombinant IL-2 (5000 U/mL).

Results: The presence of the IL-2 receptor in hepatocytes was shown by immunoblots, flow cytometry, and scanning confocal microscopy. IL-2 caused a 46% decrease in total cytochrome P450; a 35%, 35%, 36%, 26%, and 56% decrease in immunoreactive cytochrome P4501A1, 2B, 2C11, 2D1, and 3A, respectively; and a marked decrease in cytochrome P4503A2 and 2C11 messenger RNAs. Addition to the culture medium of the anti-receptor antibody or the tyrosine kinase inhibitor genistein prevented the IL-2-mediated decrease in cytochrome P450.

Conclusions: IL-2 down-regulates the expression of cytochrome P450 genes in cultured rat hepatocytes by interacting with its receptor expressed on hepatocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Base Sequence
  • Cells, Cultured
  • Cytochrome P-450 Enzyme System / metabolism*
  • Down-Regulation
  • Flow Cytometry
  • Genistein
  • Humans
  • Immunoblotting
  • Interleukin-2 / genetics
  • Interleukin-2 / physiology
  • Isoflavones / pharmacology
  • Liver / cytology
  • Liver / metabolism*
  • Male
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-2 / physiology*


  • Antibodies, Monoclonal
  • Interleukin-2
  • Isoflavones
  • RNA, Messenger
  • Receptors, Interleukin-2
  • Cytochrome P-450 Enzyme System
  • Genistein
  • Protein-Tyrosine Kinases