Iwanami M, Takeda K, Iwamoto S, Konno K
First Department of Biochemistry, School of Medicine, Showa University, Tokyo.
Jpn J Cancer Res. 1990 May;81(5):520-6. doi: 10.1111/j.1349-7006.1990.tb02601.x.
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.
我们研究了γ干扰素（IFN-γ）与霍乱毒素的联合作用以及环磷酸腺苷（cAMP）在诱导一个对分化不敏感的U-937克隆分化中的作用，该克隆对分化诱导剂的反应性降低。单独使用IFN-γ（100单位/毫升）或霍乱毒素（10^(-9) M）仅轻微诱导各种与分化相关的特性，如硝基蓝四唑（NBT）还原活性、吞噬活性、α-萘乙酸酯酶活性和表面标志物。然而，当它们相互联合时，则显著诱导这些标志物。其他诱导cAMP的试剂，如前列腺素E2、福斯高林、肾上腺素和异丙肾上腺素，单独或与IFN-γ联合使用时均未诱导NBT还原活性。然而，所有这些诱导cAMP的试剂均显著提高细胞内cAMP水平。单独使用肿瘤坏死因子、白细胞介素6或粒细胞/巨噬细胞集落刺激因子不会诱导NBT还原活性，但与霍乱毒素联合使用时可诱导活性。这些结果表明，霍乱毒素与IFN-γ或其他细胞因子联合使用增强分化诱导作用可能不仅仅是由于cAMP水平升高。似乎存在除cAMP之外的与霍乱毒素偶联的转导信号来刺激不敏感的U-937克隆的分化诱导。
