IFN-gamma treatment increases insulin binding and MHC class I expression in erythroleukemia cells

Immunol Invest. Jan-Mar 1996;25(1-2):37-47. doi: 10.3109/08820139609059289.


We have investigated if interferon-gamma (IFN-gamma) treatment of human K562 tumor cells, which upregulates the expression of MHC class I antigens (MHC-I), simultaneously would influence insulin binding. Treatment of K562 cells with recombinant human IFN-gamma for 48 h caused a significant increase of insulin binding at 37 degrees C. Recombinant human tumor necrosis factor-alpha (TNF-alpha) alone had no effect but acted synergistically with IFN-gamma, leading to a two-fold increase of insulin binding. No change in affinity, number of binding sites or cell surface expression of insulin receptors (IR) after IFN-gamma treatment could be detected. The increased insulin binding observed at 37 degrees C was not seen at 4 degrees C, suggesting alteration of insulin internalization. The dose-response curve, as well as the time curve, for the increase in insulin binding after IFN-gamma treatment correlated with enhanced cell surface expression of MHC-I antigens. However, the correlation was not absolute. Our results show that IFN-gamma treatment alone or together with TNF-alpha, can alter the insulin binding to K562 cells without changing the expression or affinity of the IR. This correlates with the effect of IFN-gamma on MHC-I expression. These results support the findings that MHC-I molecules associate and interact with the IR at the cell surface.

Publication types

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

MeSH terms

  • Endocytosis / drug effects
  • HLA Antigens / metabolism*
  • Humans
  • Insulin / metabolism*
  • Interferon-gamma / pharmacology*
  • Leukemia, Erythroblastic, Acute / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Macromolecular Substances
  • Neoplasm Proteins / metabolism
  • Protein Binding / drug effects
  • Receptor, Insulin / drug effects
  • Receptor, Insulin / metabolism*
  • Recombinant Proteins / pharmacology
  • Tumor Cells, Cultured / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology


  • HLA Antigens
  • Insulin
  • Macromolecular Substances
  • Neoplasm Proteins
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Receptor, Insulin