Glucocorticoid Receptor Mediates the Effect of Progesterone on Uterine Natural Killer Cells
Glucocorticoid Receptor Mediates the Effect of Progesterone on Uterine Natural Killer Cells
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DOI：
10.1111/j.1600-0897.2012.01114.x
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发表时间：
2012-06-01
影响因子：
3.6
通讯作者：
Hou, Yayi
中科院分区：
文献类型：
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作者：
Guo, Wei;Li, Pengfei;Hou, Yayi
问题 子宫自然杀伤细胞 (uNK) 不表达孕激素受体，但表达糖皮质激素受体 (GR)。因此，我们推测黄体酮可能通过 GR 介导的过程来调节 uNK 细胞。研究方法在存在或不存在孕酮预处理的情况下，用含有或不含有IL-12的CpG刺激小鼠NK细胞后，使用RU486（孕酮受体和GR拮抗剂）和CDB-2914（孕酮受体拮抗剂）研究孕酮通过GR对NK的影响。 CD69和IFN-γ的表达情况通过流式细胞术和 qPCR 测定。 IκB 和STAT4 的磷酸化通过Western blot 测定。此外，我们使用抗CD56微珠从人类蜕膜组织中纯化了uNK细胞，以验证黄体酮通过GR对uNK的影响。结果 黄体酮抑制 CD69 和 IFN-α CpG联合IL-12诱导小鼠脾NK细胞和人uNK细胞的表达。 CDB-2914对IFN-γ没有影响。黄体酮的表达受到抑制，而RU486可以消除黄体酮的抑制作用。此外，孕酮还可降低 STAT4 和 IκB 的磷酸化。结论在本研究中，我们首先证明孕酮可以通过GR调节NK细胞。这对于进一步了解uNK在黄体酮调节妊娠过程中的作用具有重要意义。
Problem Uterine natural killer cells (uNK) do not express progesterone receptor, but express glucocorticoid receptor (GR). So, we speculate that progesterone may regulate uNK cells through a GR-mediated process. Method of Study After mouse NK cells were stimulated with CpG with or without IL-12 in the presence or absence pre-treatment of progesterone, the effects of progesterone on NK via GR were investigated by using RU486 (progesterone receptor and GR antagonist) and CDB-2914 (progesterone receptor antagonist). The expressions of CD69 and IFN-? were determined by flow cytometry and qPCR. Phosphorylation of I?B and STAT4 was determined by Western blot. Furthermore, we purified uNK cells from human decidual tissues using anti-CD56 microbeads to verify the effect of progesterone on uNK via GR. Results Progesterone suppressed CD69 and IFN-? expression of mouse spleen NK cells and human uNK cells induced by CpG combined with IL-12. CDB-2914 had no effect on IFN-? expression suppressed by progesterone, while RU486 could abolish the inhibitory effect of progesterone. In addition, progesterone could decrease the phosphorylation of both STAT4 and I?B. Conclusions In the present study, we first prove that progesterone can regulate NK cells via GR. It is valuable for further understanding the role of uNK in progesterone regulated gestation process.