Both type I and type II interferons down-regulate human tumor necrosis factor receptors in human hepatocellular carcinoma cell line Hep G2. Role of protein kinase C

FEBS Lett. 1994 Jan 3;337(1):99-102. doi: 10.1016/0014-5793(94)80637-3.

Abstract

It is well known that interferon-gamma (IFN-gamma; type II) potentiates various responses of human tumor necrosis factor (TNF) in a wide variety of cells and that this potentiation is accompanied by the up-regulation of TNF receptor synthesis. In the present studies we examined the regulation of TNF receptors by type I and type II IFNs in a hepatocellular carcinoma cell line, HEP G2. Exposure of these cells to IFN-gamma led to a decrease in TNF receptor number (4029 vs. 2719 sites/cell) without any change in the receptor affinity (0.96 nM vs. 1.1 nM). The effect was time and dose-dependent. Like IFN-gamma, IFN-alpha and IFN-beta (type I) down-modulated the TNF receptors on these cells. The effect of IFNs on the TNF receptors was inhibited by staurosporin, a protein kinase C (PK-C) inhibitor. Furthermore, by the use of receptor-specific antibodies, we found that the IFN-dependent decrease was primarily due to the p60 form of the TNF receptor. Our results presented are the first to demonstrate that IFNs can also down-modulate TNF receptors in certain cells and that this effect is mediated through PK-C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Carcinoma, Hepatocellular / metabolism*
  • Down-Regulation* / drug effects
  • Humans
  • Interferon Type I / pharmacology*
  • Interferon-alpha / pharmacology
  • Interferon-beta / pharmacology
  • Interferon-gamma / pharmacology*
  • Liver Neoplasms / metabolism*
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Staurosporine
  • Tumor Cells, Cultured

Substances

  • Alkaloids
  • Interferon Type I
  • Interferon-alpha
  • Receptors, Tumor Necrosis Factor
  • Interferon-beta
  • Interferon-gamma
  • Staurosporine