IFN-gamma treatment increases insulin binding and MHC class I expression in erythroleukemia cells.
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.
Ferm
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Department of Immunology, Karolinska Institutet, Stockholm, Sweden.
Grönberg
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Tally
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D004705:Endocytosis / Q000187:drug effects; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology; D046911:Macromolecular Substances; D009363:Neoplasm Proteins / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D006680:HLA Antigens; D007328:Insulin; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011972:Receptor, Insulin