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首页> 外文期刊>Journal of Cellular Physiology >Arecoline-induced death of human leukemia K562 cells is associated with surface up-modulation of TNFR2
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Arecoline-induced death of human leukemia K562 cells is associated with surface up-modulation of TNFR2

机译:人类白血病K562 Arecoline-induced死亡细胞与表面up-modulation相关联TNFR2

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The goal of the present study is to explore the contribution of tumor necrosis factor-α (TNFα)-related pathway to the cytotoxicity of arecoline on human leukemia K562 cells. Arecoline treatment induced death of K562 cells and increased surface expression of TNFα, TNFR1, and TNFR2. Unlike that of TNFR1 mRNA, transcriptional levels of TNFα and TNFR2 mRNA increased in arecoline-treated cells. Moreover, arecoline-induced down-regulation of ADAM17 maturation was involved in surface up-modulation of TNFR1, TNFR2, and TNFα. Arecoline-elicited increase in intracellular Ca 2+ concentration was responsible for JNK/c-Jun pathway activation and ERK inactivation. Abolition of JNK/c-Jun pathway suppressed arecoline-induced increase in transcriptional level of TNFα and TNFR2 mRNA. TNFα and TNFR2 promoter luciferase activity and chromatin immunoprecipitating analyses revealed that c-Jun increasingly bound with TNFα and TNFR2 promoter upon arecoline treatment. Over-expression of constitutively active MEK1 abolished the effect of arecoline on suppressing ADAM17 maturation. Pretreatment with TNFR2 antibody abrogated arecoline-induced increased susceptibility of K562 cells for the cytotoxicity of TNFα and arecoline-induced cell death. Taken together, our data suggest that up-modulation of TNFR2 surface expression is associated with arecoline-induced death of K562 cells.
机译:本研究的目的是探索肿瘤坏死因子-α的贡献(肿瘤坏死因子α)-相关通路的细胞毒性槟榔碱对人类白血病K562细胞。治疗诱导K562细胞的死亡增加表面的肿瘤坏死因子α的表达,TNFR1,TNFR2。肿瘤坏死因子α和TNFR2 mRNA水平增加arecoline-treated细胞。arecoline-induced ADAM17下调成熟up-modulation参与表面TNFR1 TNFR2,肿瘤坏死因子α。增加细胞内钙浓度2 +负责物/ c-Jun途径激活ERK失活。抑制arecoline-induced增加肿瘤坏死因子α和TNFR2 mRNA转录水平。肿瘤坏死因子α和TNFR2启动子荧光素酶活性染色质免疫沉淀反应分析显示与肿瘤坏死因子α和TNFR2 c-Jun越来越束缚启动子在槟榔碱治疗。表达的MEK1持续活跃废除了槟榔碱对抑制的影响ADAM17成熟。抗体废除arecoline-induced增加易感性K562细胞的细胞毒性肿瘤坏死因子α和arecoline-induced细胞死亡。在一起,我们的数据表明,up-modulationTNFR2表面表达有关arecoline-induced K562细胞的死亡。

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