IFN-GAMMA TREATMENT INCREASES INSULIN BINDING AND MHC CLASS-I EXPRESSION IN ERYTHROLEUKEMIA-CELLS

We have investigated if interferon-gamma (IFN-gamma) treatment of huma n K562 tumor cells, which upregulates the expression of MHC class I an tigens (MHC-I), simultaneously would influence insulin binding. Treatm ent of K562 cells with recombinant human IFN-gamma for 48 h caused a s ignificant increase of insulin binding at 37 degrees C. Recombinant hu man tumor necrosis factor-alpha (TNF-alpha) alone had no effect but ac ted synergistically with IFN-gamma, leading to a two-fold increase of insulin binding. No change in affinity, number of binding sites or cel l surface expression of insulin receptors (IR) after IFN-gamma treatme nt could be detected. The increased insulin binding observed at 37 deg rees C was not seen at 4 degrees C, Suggesting alteration of insulin i nternalization. The dose-response curve, as well as the time curve, fo r 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 treatme nt 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 re sults support the findings that MHC-I molecules associate and interact with the IR at the cell surface.