Yoshida M, Eguchi T, Ikekawa N, Saijo N
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
J Interferon Cytokine Res. 1995 Nov;15(11):965-71. doi: 10.1089/jir.1995.15.965.
The combined effects of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] and interferon-gamma (IFN-gamma) or tumor necrosis factor alpha (TNF-alpha) on cell differentiation in HL-60 human promyelocytic leukemia cells were examined by a nitroblue tetrazolium (NBT) reduction test. 1,25(OH)2D3 at the concentrations of 7-70 nM induced NBT-positive cells, which was used as a criterion of cell differentiation. IFN-gamma itself showed little effect on induction of NBT-positive cells or on cell growth at a concentration up to 1000 U/ml. However, in a combination of 1,25(OH)2D3 with IFN-gamma (100 and 300 U/ml), cell differentiation was strongly inhibited and was accompanied by growth inhibition. Treatment with a combination of 1,25(OH)2D3 and TNF-alpha or IFN-gamma and TNF-alpha showed an additive effect on cell differentiation. IFN-gamma seems to act as a specific inhibitor for 1,25(OH)2D3-induced cell differentiation. To elucidate the cause of the inhibition of cell differentiation by IFN-gamma, the ability of the cells to produce superoxide (O2-) was examined after culture for 5 days in the presence of 1,25(OH)2D3 and IFN-gamma. The results indicated that the inhibition of IFN-gamma was caused by a reduction in the ability of the cells to produce O2- in response to stimulation by 12-O-tetradecanoylphorbol-13-acetate (TPA).
通过硝基蓝四氮唑（NBT）还原试验，研究了1α,25-二羟基维生素D3[1,25(OH)2D3]与干扰素-γ（IFN-γ）或肿瘤坏死因子-α（TNF-α）联合作用对HL-60人早幼粒细胞白血病细胞分化的影响。浓度为7-70 nM的1,25(OH)2D3可诱导NBT阳性细胞，以此作为细胞分化的标准。在浓度高达1000 U/ml时，IFN-γ本身对NBT阳性细胞的诱导或细胞生长几乎没有影响。然而，1,25(OH)2D3与IFN-γ（100和300 U/ml）联合使用时，细胞分化受到强烈抑制，并伴有生长抑制。1,25(OH)2D3与TNF-α或IFN-γ与TNF-α联合处理对细胞分化显示出相加作用。IFN-γ似乎是1,25(OH)2D3诱导的细胞分化的特异性抑制剂。为了阐明IFN-γ抑制细胞分化的原因，在1,25(OH)2D3和IFN-γ存在的情况下培养5天后，检测了细胞产生超氧化物（O2-）的能力。结果表明，IFN-γ的抑制作用是由于细胞对12-O-十四酰佛波醇-13-乙酸酯（TPA）刺激产生O2-的能力降低所致。
