Enhancement of interferon-gamma-induced differentiation of human monoblastic leukemia U-937 cells by cAMP-inducing agents.
The effects of combinations of interferons (IFNs) and cAMP-inducing agents on the induction of differentiation of human monocytic leukemia U-937 cells were examined. IFN-gamma induced nitro blue tetrazolium (NBT) reducing activity of U-937 cells in a dose-dependent manner, while cAMP-inducing agents such as cholera toxin, prostaglandin E1, forskolin, and isoproterenol only marginally induced NBT reducing activity. However, they all synergistically increased IFN-gamma induction of NBT reducing activity. Cholera toxin was the most potent of the cAMP-inducing agents. Combination effects of IFN-gamma and cholera toxin on other differentiation-associated markers of alpha-naphthyl acetate esterase activity, morphological maturation, Fc receptors, and surface phenotype were also observed. IFN-alpha and -beta, either alone or in combination with cAMP-inducing agents, did not induce NBT reducing activity. IFN-gamma and cholera toxin also synergistically induced differentiation-associated markers in another human monocytic leukemia cell line, THP-1, and a human myeloblastic leukemia cell line, ML-1. These results suggest that cAMP/A-kinase may be an important but insufficient signal for the maturation process of myelogenous leukemia cells.
First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.
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Iwanami
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Takeda
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Konno
D000527:Alprostadil / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007372:Interferons / Q000494:pharmacology; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism / Q000473:pathology*; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured
D009580:Nitroblue Tetrazolium; D007371:Interferon-gamma; D007372:Interferons; D002772:Cholera Toxin; D000242:Cyclic AMP; D000527:Alprostadil