Interferon-inducible gene expression in HL-60 cells: effects of the state of differentiation

The promyelocytic leukemia line HL-60 can be terminally differentiated in vitro to either monocyte/macrophages or granulocytes. We used this cell line to test whether the state of differentiation of a cell changes its response to interferon (IFN). The characteristics of expression of several IFN-alpha- and IFN-gamma-inducible genes in undifferentiated and differentiated HL-60 cells were examined. p67, an IFN-gamma-inducible protein, was induced similarly in three cell types, whereas another IFN-gamma-inducible protein, p56, was induced strongly only in undifferentiated cells. In contrast, two isozymes of 2,5(A)-synthetase were induced better in differentiated cells in response to either IFN. Several IFN-alpha-inducible mRNAs, e.g., 561, 6-16, 1-8, and 2A, were induced much more strongly in granulocytes than in macrophages or in undifferentiated cells. Electrophoretic mobility shift assays using the IFN-stimulated response element of gene 561 and nuclear extracts of IFN-alpha-treated cells revealed the appearance of one complex and the disappearance of another one, concomitant with differentiation of the cells to granulocytes. These observations suggest that expression of IFN-inducible genes in HL-60 cells is regulated by trans-acting factors whose activity changes with the state of differentiation of the cells. Our study may have implications in the optimal clinical use of IFNs. Inducing cellular differentiation may augment the efficacy of IFNs as antitumor agents.