Department of Microbiology and Brain Korea 21 PLUS project for Medical science, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
Cell Immunol. 2014 Jul;290(1):52-61. doi: 10.1016/j.cellimm.2014.05.001. Epub 2014 May 13.
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.
自然杀伤 (NK) 细胞在癌症患者中受到抑制的主要因素和机制尚未得到很好的定义。在这项研究中，我们对 TGF-β、IL-10 和 IL-4 对原代 NK 细胞的影响进行了比较分析，结果表明：(1) TGF-β 最有效地抑制 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 TGF-β 处理也完全抑制了 IL-2 诱导的 C-myb、AP-1、CREB 和 AR 的启动子结合活性。有趣的是，TGF-β 还完全抑制了其他组成性激活的转录因子。在这些因子中，我们通过 c-jun 和 MEK1 抑制剂测定进一步证实了 AP-1 在 NK-92 细胞激活中的作用。我们的研究深入了解了 TGF-β 在调节 NK 细胞功能方面的作用。
