Modulation of 17β-estradiol on the number and cytotoxicity of NK cells in vivo related to MCM and activating receptors
Modulation of 17β-estradiol on the number and cytotoxicity of NK cells in vivo related to MCM and activating receptors
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DOI：
10.1016/j.intimp.2007.09.017
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发表时间：
2007-12-15
影响因子：
5.6
通讯作者：
Hou, Yayi
中科院分区：
文献类型：
--
作者：
Hao, Sha;Zhao, Junli;Hou, Yayi
自然杀伤细胞（NK）是免疫系统的重要组成部分，其活性受性激素的调控。在本研究中，我们研究了雌激素对体内NK细胞数量和细胞毒活性的影响。测定4组（对照组、sham+对照、Ovx+对照、Ovx+对照、Ovx+E2） NK细胞数量及细胞毒性。结果表明，17 -雌二醇（E2）增加NK细胞数量，但降低NK细胞的细胞毒性。E2对NK细胞比例的增加可能是通过上调MCM7和MCM10蛋白的表达来介导的，MCM7和MCM10蛋白是细胞增殖中DNA复制许可所必需的。E2抑制脾脏NK细胞的细胞毒性可能是由于下调NK细胞活化受体cd69、NKp46、NKG2DL和2134 (CD244)，直接抑制NK细胞的活化，导致可溶性因子颗粒酶B和FasL的分泌减少。nf - γ也可能在NK细胞的低细胞毒性中起负调节作用。此外，体内长期暴露于E2的NK细胞数量与其细胞毒性不平行。这些结果提示e2介导的NK细胞的低细胞毒性可能调节宿主在妊娠期和一些女性显性疾病中的免疫反应。(c) 2007年Elsevier b.v.出版。
Natural killer (NK) cells are key components of immune systems and their activities could be regulated by sex hormones. In the present study we investigate the effects of estrogen on the number and cytotoxic activity of NK cells in vivo. The number and cytotoxicity of NK cells in four groups (control, sham+vehicle, Ovx+vehicle and Ovx+E2) were determined. The results showed that 17 beta-estradiol (E2) increased the number of NK cells, but reduced their cytotoxicity. The increase of NK cells proportions by E2 may be mediated by upregulating the expression of MCM7 and MCM10 proteins, which are required for DNA replication licensing in cell proliferation. The suppressed cytotoxicity of splenic NK cells by E2 may be attributable to the down-regulation of NK cells activating receptors-CD69, NKp46, NKG2DL and 2134 (CD244), which directly inhibited NK cell activation, resulting in the reduced secretion of the soluble factors-granzyme B and FasL. INF-gamma might also act as a negative regulator in the low cytotoxicity of NK cells. In addition, the number of the NK cells is not parallel to their cytotoxicity with a long-term exposure to E2 in vivo. These results suggest that E2-mediated low cytotoxicity of NK cells may regulate host immune response in pregnancy and some female predominant diseases. (c) 2007 Published by Elsevier B.V..