Effects of cytokines on synthesis and function of the hepatic asialoglycoprotein receptor

J Cell Physiol. 1994 Mar;158(3):527-34. doi: 10.1002/jcp.1041580319.


In this study we have investigated whether cytokines, critical mediators of the immune response, might have a direct effect on the expression and/or function of the human hepatic asialoglycoprotein receptor (ASGPR). Binding and uptake of asialoglycoproteins by the human hepatoma cell line, HepG2, and by freshly isolated rat hepatocytes were inhibited by 50% after 3-6 hours and completely abolished following a 24 hour exposure to tumor necrosis factor (TNF) alpha, interferon (INF) alpha or gamma, or interleukin-2 (IL-2). The loss of ASGPR binding activity mediated by IL-2 was reversible up to 4 hours of exposure and accompanied by the selective phosphorylation of the cell-surface receptor. Steady-state levels of total cellular ASGPR protein remained unchanged over the first 6 hours of IL-2 incubation but declined in a dose dependent manner thereafter. This down regulation of ASGPR expression was due to reduced synthesis as a result of reduced receptor transcript levels. No loss was detected, however, of cell surface-associated receptor protein even after 24 hours of IL-2 incubation, suggesting that cytokine induced phosphorylation constitutes a mechanism to regulate receptor activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibody Formation
  • Asialoglycoprotein Receptor
  • Asialoglycoproteins / metabolism
  • Carcinoma, Hepatocellular / chemistry
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / ultrastructure
  • Cytokines / pharmacology*
  • Down-Regulation
  • Humans
  • Interferon-alpha / pharmacology
  • Interferon-gamma / pharmacology
  • Interleukin-2 / pharmacology
  • Liver Neoplasms / chemistry
  • Liver Neoplasms / pathology
  • Liver Neoplasms / ultrastructure
  • Phosphorylation
  • Receptors, Cell Surface / analysis
  • Receptors, Cell Surface / metabolism*
  • Receptors, Cell Surface / physiology*
  • Receptors, Interleukin-2 / analysis
  • Time Factors
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology


  • Asialoglycoprotein Receptor
  • Asialoglycoproteins
  • Cytokines
  • Interferon-alpha
  • Interleukin-2
  • Receptors, Cell Surface
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma