INHIBITION OF ERYTHROPOIETIN PRODUCTION IN-VITRO BY HUMAN INTERFERON-GAMMA
INHIBITION OF ERYTHROPOIETIN PRODUCTION IN-VITRO BY HUMAN INTERFERON-GAMMA
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DOI：
10.1111/j.1365-2141.1994.tb04864.x
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发表时间：
1994-05-01
影响因子：
6.5
通讯作者：
ROSSIFERRINI, P
中科院分区：
文献类型：
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作者：
VANNUCCHI, AM;GROSSI, A;ROSSIFERRINI, P
研究了干扰素- γ (ifn - γ)单独或联合IL-1、IL-6和肿瘤坏死因子- α (tnf - α)对人肝癌Hep3B细胞株体外促红细胞生成素（Epo）生成的影响。将ifn - γ添加到未刺激或氯化钴（CoCl2）处理的Hep3B细胞中，在1000 U/ml时，培养基中Epo释放的剂量依赖性抑制高达70%。在50 U/ml左右观察到半最大抑制。根据先前的观察，IL-6对cocl2处理的Hep3B细胞的Epo产生有刺激作用；然而，同时加入ifn - γ和IL-6导致IL-6的刺激作用逆转。ifn - γ和IL-1具有加性抑制作用，而ifn - γ和tnf - α以协同方式抑制Hep3B细胞的Epo产生。Northern blot分析显示，ifn - γ的抑制作用似乎是由于cocl2处理的Hep3B细胞中Epo mRNA水平的下调。这些数据表明，体外培养的肝癌细胞产生促生成素受到ifn - γ的抑制，一个复杂的相互作用的细胞因子网络可能在缺氧刺激下调节促生成素的产生。总的来说，这些结果还表明，ifn - γ可能在几种炎症和免疫介导的以相对较高的ifn - γ血浆水平为特征的疾病中观察到的Epo产生缺陷中起作用。
The effects of interferon-gamma (IFN-gamma), alone and in combination with IL-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha), on in vitro erythropoietin (Epo) production by the human hepatoma Hep3B cell line were evaluated. The addition of IFN-gamma to either unstimulated or cobalt chloride (CoCl2)-treated Hep3B cells resulted in a dose-dependent inhibition of Epo release in the medium by as much as 70% at 1000 U/ml. Half-maximal inhibition was observed at around 50 U/ml. According to previous observations, IL-6 had a stimulatory effect on Epo production by CoCl2-treated Hep3B cells; however, the simultaneous addition of IFN-gamma and IL-6 resulted in a reversal of the stimulatory effects due to IL-6. IFN-gamma and IL-1 had an additive inhibitory effect, whereas IFN-gamma and TNF-alpha acted in a synergistic fashion in inhibiting Epo production by Hep3B cells. The inhibitory effect of IFN-gamma appeared to be due to a down-modulation of Epo mRNA levels in CoCl2-treated Hep3B cells, as shown by Northern blot analysis.These data indicate that Epo production by hepatoma cells in vitro is inhibited by IFN-gamma, and that a complex network of interacting cytokines may regulate Epo production in response to an hypoxic stimulus. Overall, these results also suggest that IFN-gamma might have a role in the defective Epo production observed in several inflammatory and immune-mediated disorders characterized by relatively high IFN-gamma plasma levels.