Role of endoplasmic reticulum stress in lipopolysaccharide-inhibited mouse granulosa cell estradiol production
Role of endoplasmic reticulum stress in lipopolysaccharide-inhibited mouse granulosa cell estradiol production
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内质网应激在脂多糖抑制小鼠颗粒细胞雌二醇产生中的作用
DOI：
10.1262/jrd.2019-052
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发表时间：
2019-10-01
影响因子：
1.8
通讯作者：
Yang, Lei
中科院分区：
文献类型：
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作者：
Lei, Lanjie;Ge, Junbang;Yang, Lei
脂多糖(LPS)引起的颗粒细胞雌二醇(E-2)水平下降是产后子宫感染导致不孕的主要原因之一，其确切的分子机制尚不清楚。本研究探讨内质网应激在脂多糖诱导的小鼠颗粒细胞雌二醇性激素水平下降中的作用。我们的结果显示，内毒素增加了促炎细胞因子[白介素1β、白介素6、白介素8和肿瘤坏死因子α]，激活了内质网应激标志物蛋白的表达[葡萄糖调节蛋白78(GRP78)和CCAAT/增强子结合蛋白同源蛋白(CHOP)]，降低了细胞色素P450家族19亚家族A成员1(CYP19A1)的表达和E-2的产生。此外，4-苯基丁酸酯(4-PBA)抑制内质网应激可减弱Thapsigargin(TG，内质网应激激动剂)或内毒素诱导的Cypl 9A1和E2的减少，以及促炎细胞因子(IL-1β、1L-6、IL-8和TNF-α)的表达，以及CHOP和GRP78的表达。此外，雷诺洛韦(TAK-242)对Toll样受体4(TLR4)的抑制可逆转内毒素对细胞色素P19A1的表达和E2的产生、对GRP78和CHOP的激活以及对IL-1β、IL-6、IL-8和TNF-α表达的抑制作用。综上所述，我们的研究表明，内质网应激参与了内毒素抑制的小鼠颗粒细胞产生E-2。
The decrease in the level of estradiol (E-2) in granulosa cells caused by lipopolysaccharide (LPS) is one of the major causes of infertility underlying postpartum uterine infections; the precise molecular mechanism of which remains elusive. This study investigated the role of endoplasmic reticulum (ER) stress in LPS-induced E-2 decrease in mouse granulosa cells. Our results showed that LPS increased the pro-inflammatory cytokines [(interleukin (IL)-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha)], activated ER stress marker protein expression [(glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP)], and decreased cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) expression and E-2 production. Moreover, inhibition of ER stress by 4-phenylbutyrate (4-PBA) attenuated thapsigargin-(TG, ER stress agonist) or LPS-induced reduction of Cypl 9a1 and E2, pro-inflammatory cytokines expression (IL-1 beta, 1L-6, IL-8, and TNF-alpha), and the expression of CHOP and GRP78. Additionally, inhibition of toll-like receptor 4 (TLR4) by resatorvid (TAK-242) reversed the inhibitory effects of LPS on Cyp19a1 expression and E2 production, activation of GRP78 and CHOP, and expression of IL-1 beta, IL-6, IL-8, and TNF-alpha. In summary, our study suggests that ER stress is involved in LPS-inhibited E-2 production in mouse granulosa cells.