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A comparative study of the effects of inhibitory cytokines on human natural killer cells and the mechanistic features of transforming growth factor-beta

机译:抑制性细胞因子对人类自然杀伤细胞作用及转化生长因子-β机理的比较研究

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The major factors and mechanisms by which natural killer (NK) cells are inhibited in cancer patients have not yet been well defined. In this study, we conducted a comparative analysis of the effects of TGF-β, IL-10, and IL-4 on primary NK cells, and it was demonstrated that (1) TGF-β most potently inhibited the overall function of NK cells. (2) It appears that TGF-β reduced the tyrosine phosphorylation of Syk and the expression of c-myc. (3) It was also found that the IL-2-induced promoter-binding activities of C-myb, AP-1, CREB, and AR were also completely suppressed upon TGF-β treatment. Interestingly, TGF-β also completely suppressed other transcription factors, which are constitutively activated. Among these factors, we further confirmed roles of AP-1 in NK-92 cell activation through c-jun and MEK1 inhibitor assay. Our study provides insight into the effects of TGF-β in modulating NK cell functions.
机译:癌症患者抑制自然杀伤(NK)细胞的主要因素和机制尚未明确。在这项研究中,我们对TGF-β,IL-10和IL-4对原代NK细胞的作用进行了比较分析,结果表明(1)TGF-β最有效地抑制了NK细胞的整体功能。 (2)似乎TGF-β降低了Syk的酪氨酸磷酸化和c-myc的表达。 (3)还发现,通过TGF-β处理,IL-2诱导的C-myb,AP-1,CREB和AR的启动子结合活性也被完全抑制。有趣的是,TGF-β也完全抑制了组成型激活的其他转录因子。在这些因素中,我们进一步通过c-jun和MEK1抑制剂分析证实了AP-1在NK-92细胞活化中的作用。我们的研究提供了对TGF-β在调节NK细胞功能中作用的见解。

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