Combination Effects of Interferon‐γ and Cholera Toxin on Induction of Differentiation of an Insensitive U‐937 Clone

We examined the combination effect of interferon‐γ (IFN‐γ) 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‐γ (100 units/ml) or cholera toxin (10(–9)M) alone only marginally induced various differentiation‐associated characteristics such as NBT‐reducing activity, phagocytic activity, α‐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 E(2), forskolin, epinephrine and isoproterenol did not induce NBT‐reducing activity, either alone or in combination with IFN‐γ. 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‐γ 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.