Mechanism of Decrease in Transferrin Receptor Synthesis by Interferon-α Treated Human Lymphoblastoid Cells

Abstract

To clarify the mechanism of antiproliferative action of interferon-α (IFN-α) in hematological malignancy, we examined the transferrin receptor system in the lymphoblastoid cell line, Daudi cells treated with IFN-α. When cells were cultured with 10(4)U/ml of IFN-α, the number of surface transferrin receptors was decreased to 60% of that seen in the control culture. This decrease was not neutralized by co-incubation with the iron chelator, desferrioxamine (10-200 μM), suggesting that the change in the level of chelatable iron did not account for the decrease in transferrin receptor numbers. When determined by metabolic labeling using (35)S-methionine, IFN-α markedly decreased the rate of transferrin receptor biosynthesis. Uptake of iron and the cellular ferritin content also decreased by 50% when incubated with 10(4)U/ml of IFN-α. These data indicate that IFN-α inhibits transferrin receptor biosynthesis in an iron-independent fashion and the subsequent cellular iron-deficiency state may play a role in the antiproliferative action of IFN-α.