IL-1β Upregulates StAR and Progesterone Production Through the ERK1/2-and p38-Mediated CREB Signaling Pathways in Human Granulosa-Lutein Cells
IL-1β Upregulates StAR and Progesterone Production Through the ERK1/2-and p38-Mediated CREB Signaling Pathways in Human Granulosa-Lutein Cells
复制标题
IL-1 beta 通过 ERK1/2 和 p38 介导的 CREB 信号通路上调人颗粒叶黄素细胞中 StAR 和孕酮的产生
DOI：
10.1210/en.2017-00029
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发表时间：
2017-10-01
期刊：
影响因子：
4.8
通讯作者：
Sun, Yun
中科院分区：
文献类型：
--
作者：
Dang, Xuan;Zhu, Qinling;Sun, Yun
促炎细胞因子白细胞介素-1 β（IL-1 β）可能参与几个排卵相关事件，如蛋白酶合成、前列腺素产生和颗粒细胞中的类固醇生成。然而，IL-1 β对颗粒细胞孕酮合成的确切作用及其机制尚不清楚。通过使用从接受体外受精或卵胞浆内单精子注射的妇女收集的培养的颗粒体-黄体细胞，我们发现IL-1 β上调颗粒体-黄体细胞中类固醇生成急性调节蛋白（星星）的表达和孕酮的合成，这与促黄体生成激素的作用相当，并且可以被IL-1受体拮抗剂消除。此外，IL-1 β激活磷酸化的环磷酸腺苷反应元件结合蛋白（CREB），和敲低CREB减弱诱导的星星表达和孕酮合成的IL-1 β在颗粒黄体细胞。此外，IL-1 β激活细胞外信号调节激酶（ERK）1/2和p38途径，抑制ERK 1/2和p38途径减弱了IL-1 β诱导的CREB磷酸化、星星表达和颗粒黄体细胞中的孕酮合成。总之，IL-1 β可通过激活ERK 1/2和p38通路，通过增加CREB磷酸化，上调星星表达，刺激人颗粒体-黄体细胞中孕酮的生物合成。
The proinflammatory cytokine interleukin-1 beta (IL-1 beta) may be involved in several ovulation-associated events, such as protease synthesis, prostaglandin production, and steroidogenesis in granulosa cells. However, the exact effect of IL-1 beta on progesterone synthesis in granulosa cells and the underlying mechanism remain unclear. By using cultured granulosa-lutein cells collected from women undergoing in vitro fertilization or intracytoplasmic sperm injection, we found that IL-1 beta upregulated steroidogenic acute regulatory protein (StAR) expression and progesterone synthesis in granulosa-lutein cells, which was comparable with luteinizing hormone effect and could be abolished by an IL-1 receptor antagonist. Moreover, IL-1 beta activated the phosphorylation of cyclic adenosine monophosphate response element-binding protein (CREB), and knockdown of CREB attenuated the induction of StAR expression and progesterone synthesis by IL-1 beta in granulosa-lutein cells. Furthermore, IL-1 beta activated the extracellular signal-regulated kinase (ERK)1/2 and p38 pathways and inhibition of the ERK1/2 and p38 pathways attenuated the IL-1 beta-induced phosphorylation of CREB, StAR expression, and progesterone synthesis in granulosa-lutein cells. In conclusion, IL-1 beta could upregulate StAR expression and stimulate progesterone biosynthesis through increase in CREB phosphorylation via activating the ERK1/2 and p38 pathways in human granulosa-lutein cells.