Expression of membrane progesterone receptors on human T lymphocytes and Jurkat cells and activation of G-proteins by progesterone

Expression of membrane progesterone receptors on human T lymphocytes and Jurkat cells and activation of G-proteins by progesterone
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DOI:
10.1677/joe-07-0317
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发表时间:
2008-01-01
影响因子:
4
通讯作者:
Giudice, L. C.
Giudice, L. C.
中科院分区:
医学2区
文献类型:
--
作者:
Dosiou, C.;Hamilton, A. E.;Giudice, L. C.

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尽管有明显的证据表明黄体酮。作为免疫调节剂的作用,核孕酮受体在免疫细胞中尚未被一致地鉴定。最近,已经描述了三种新的假定的膜孕酮受体(mPR),mPR α、mPR β和mPR γ。本研究的目的是检查mPR是否在育龄妇女的外周血白细胞(PBL)中表达,并进一步表征它们在T淋巴细胞和永生化T细胞(Jurkat细胞)中的特征。通过RT-PCP在PBL、T淋巴细胞和Jurkat细胞中检测到mPR α和mPR β的转录物,但未检测到mPR γ。蛋白质印迹分析显示,T淋巴细胞和Jurkat细胞的细胞膜上存在mPR α和mPR β蛋白。在月经周期的黄体期,mPR α mRNA的表达在分化簇(CD)8(+)中上调,但在CD 4(+)T淋巴细胞中不上调。放射性受体测定显示特异性[3 H]孕酮结合T-和Jurkat细胞膜(Kd 4.25 nM)的类固醇膜受体的特性。孕酮激活抑制性G蛋白(G(i)),表明mPR与Jurkat细胞中的G(i)偶联。这些结果表明,孕激素的免疫调节功能,通过激活mPRs的一个潜在的新机制。
Although there is significant evidence for progesterone's. role as an immunomodulator, nuclear progesterone receptors have not been consistently identified in immune cells. Recently, three new putative membrane progesterone receptors (mPRs), mPR alpha, mPR beta, and mPR gamma have been described. The objective of this study was to examine whether mPRs are expressed in peripheral blood leukocytes (PBLs) in women of reproductive age, and to further characterize them in T lymphocytes and immortalized T cells Jurkat cells). Transcripts for mPR alpha and mPR beta but not mPR gamma, were detected by RT-PCP in PBLs, T lymphocytes, and Jurkat cells. Western blot analysis showed the presence of the mPR alpha and mPR beta proteins on cell membranes of T lymphocytes and Jurkat cells. Expression of the mPR alpha mRNA was upregulated in the luteal phase of the menstrual cycle in cluster of differentiation (CD)8(+), but not in CD4(+), T lymphocytes. Radioreceptor assays revealed specific [3 H]progesterone binding to T- and Jurkat cell membranes (K-d 4.25 nM) characteristic of steroid membrane receptors. Progesterone activated an inhibitory G-protein (G(i)), suggesting that mPRs are coupled to G(i) in Jurkat cells. These results suggest a potential novel mechanism for progesterone's immunoregulatory function through activation of mPRs.