IFN-gamma upregulates anti-apoptotic gene expression and inhibits apoptosis in IL-3-dependent hematopoietic cells.

IFN-gamma is a cytokine which functions in a wide range of biological activities by inducing a number of early and delayed genes. In murine IL-3-dependent cell lines BAF-B03 and 32D, IFN-gamma upregulated bag-1 and bcl-xL gene expression. These cells revealed prolonged cell survival against IL-3-deprivation by IFN-gamma stimulation. In contrast, human myeloma cell line RPMI8226, despite expression of IFN-gamma receptor, showed neither induction of their expressions nor prolonged cell survival against serum starvation-induced apoptosis by IFN-gamma stimulation. Gene-transfer-mediated overexpression of BAG-1 protein in BAF-B03 cells led to prolonged cell survival against IL-3-deprived apoptosis compared with control BAF-B03 transfectants, indicating that levels of BAG-1 expression are crucial for cell survival in BAF-B03 cells. Taken together, these studies suggest that induction of anti-apoptotic gene expression is a crucial factor for the anti-apoptotic function of IFN-gamma in IL-3-dependent immature hematopoietic cells.