Combination effects of interferon-gamma and cholera toxin on induction of differentiation of an insensitive U-937 clone.
We examined the combination effect of interferon-gamma (IFN-gamma) and cholera toxin and the role of cAMP in the induction of differentiation of a differentiation-insensitive U-937 clone, in which the reactivity to differentiation-inducers was decreased. IFN-gamma (100 units/ml) or cholera toxin (10(-9) M) alone only marginally induced various differentiation-associated characteristics such as NBT-reducing activity, phagocytic activity, a-naphthyl acetate esterase activity and surface markers. However, when combined with each other, they significantly induced these markers. Other cAMP-inducing agents such as prostaglandin E2, forskolin, epinephrine and isoproterenol did not induce NBT-reducing activity, either alone or in combination with IFN-gamma. However, all these cAMP-inducing agents significantly increased intracellular cAMP levels. Tumor necrosis factor, interleukin 6 or granulocyte/macrophage colony-stimulating factor alone did not induce NBT-reducing activity, but they could induce activity when combined with cholera toxin. These results suggest that enhancement of induction of differentiation by cholera toxin in combination with IFN-gamma or other cytokines may not be merely due to increased cAMP levels. There seems to be a transduction signal other than cAMP coupling with cholera toxin to stimulate induction of differentiation of an insensitive U-937 clone.
Iwanami
M
M
First Department of Biochemistry, School of Medicine, Showa University, Tokyo.
Takeda
K
K
Iwamoto
S
S
Konno
K
K
D002454:Cell Differentiation / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology*; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D009580:Nitroblue Tetrazolium; D007371:Interferon-gamma; D002772:Cholera Toxin; D000242:Cyclic AMP