首页> 外文期刊>Life sciences >Attenuation of interferon-gamma mRNA expression in activated Jurkat T cells by exogenous zinc via down-regulation of the calcium-independent PKC-AP-1 signaling pathway.
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Attenuation of interferon-gamma mRNA expression in activated Jurkat T cells by exogenous zinc via down-regulation of the calcium-independent PKC-AP-1 signaling pathway.

机译:外源性锌通过下调非钙依赖性PKC-AP-1信号通路来减轻激活的Jurkat T细胞中干扰素-γmRNA的表达。

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摘要

Zinc is known to modulate a wide variety of cellular functions including anti-inflammatory responses. We examined the intracellular signaling pathways that contribute to the regulation of interferon-gamma (IFN-gamma) by zinc in activated human Jurkat T cells. Zinc significantly reduced IFN-gamma expression and activator protein-1 (AP-1) signaling in cells activated by phorbol 12-myristate 13-acetate (PMA) and phytohemagglutinin (PHA) without affecting cell viability. Moreover, partial inhibition of AP-1 activity by SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, resulted in marked reduction of IFN-gamma transcription. We also found that this inhibitory effect of zinc on AP-1 signaling was abolished by treatment with rottlerin, a selective inhibitor of calcium-independent protein kinase C (PKC). These results suggest a novel target of zinc in the calcium-independent protein kinase C-AP-1 pathway to regulate endogenous IFN-gamma gene expression in activated T cells.
机译:已知锌可调节多种细胞功能,包括抗炎反应。我们检查了细胞内信号通路,这些通路有助于锌激活人Jurkat T细胞中的干扰素-γ(IFN-γ)的调节。锌显着降低了佛波醇12-肉豆蔻酸酯13-醋酸酯(PMA)和植物血凝素(PHA)激活的细胞中的IFN-γ表达和激活蛋白1(AP-1)信号传导,而没有影响细胞活力。此外,SP600125是c-Jun N端激酶(JNK)抑制剂对AP-1活性的部分抑制,导致IFN-γ转录显着降低。我们还发现锌对AP-1信号的这种抑制作用已通过用rottlerin(一种钙依赖性蛋白激酶C(PKC)的选择性抑制剂)治疗而被取消。这些结果表明在钙独立蛋白激酶C-AP-1途径中锌的新靶标可调节活化T细胞中内源性IFN-γ基因的表达。

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