Effect of prostaglandin E2 on gamma-interferon and 1,25(OH)2D3 vitamin D3-induced c-myc reduction during HL-60 cell differentiation.

The effect of prostaglandin E2 (PGE2) on the reduction of c-myc expression during the differentiation of the human leukemic cell line, HL-60, was examined. PGE2, a potent inducer of intracellular cyclic AMP (cAMP) in HL-60 cells, augmented monocyte-associated cell surface antigens induced by human gamma-interferon (IFN-gamma) or 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) in these cells. The elevation of intracellular cAMP was induced dose-dependently by PGE2, but not by IFN-gamma or 1,25(OH)2D3. Changes were also seen in functional differentiation, such as, the increase of phagocytic capability and superoxide generation. PGE2 also enhanced the reduction of c-myc expression and the down-regulation of transferrin receptor by IFN-gamma or 1,25(OH)2D3, whereas PGE2 alone did not induce these phenotypic changes. These data suggest that IFN-gamma and 1,25(OH)2D3 reduce c-myc expression of HL-60 cells by a mechanism other than the augmentation of intracellular cAMP.