College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China.
Animal Science and Technology College, Beijing University of Agriculture, Beijing 102200, PR China.
Mol Immunol. 2020 Nov;127:21-30. doi: 10.1016/j.molimm.2020.08.016. Epub 2020 Sep 6.
Estrogen has known anti-inflammatory effects, but the mechanism whereby 17β-estradiol (E2) protects oviduct sheep epithelial cells from inflammation remains unknown. In this study, we detected the E2 synthetase and E2 nuclear and membrane receptors in sheep oviducts, primarily in epithelial cells. Using lipopolysaccharide (LPS)-stimulated sheep oviduct epithelial cells as an in vitro inflammation model, we demonstrated that E2 attenuates the expression of inflammatory factors in a concentration-response manner. E2 also inhibited the LPS-stimulated phosphorylation of p38 MAPK and NF-κB p65 but did not reduce the phosphorylation of JNK and ERK 1/2. This attenuation was partially antagonized by an intracellular estrogen antagonist that was involved in genomic regulation and enhanced by a G protein-coupled estrogen receptor agonist that was involved in nongenomic cellular modulation. These results suggest that E2 has an inhibitory effect on LPS-induced oviduct epithelial cell inflammation in sheep, which is mediated by the downstream regulatory effects of estrogen receptors.
雌激素具有已知的抗炎作用，但 17β-雌二醇（E2）保护输卵管绵羊上皮细胞免受炎症的机制尚不清楚。在这项研究中，我们检测了绵羊输卵管中的 E2 合成酶以及 E2 核和膜受体，主要存在于上皮细胞中。使用脂多糖（LPS）刺激的绵羊输卵管上皮细胞作为体外炎症模型，我们证明 E2 以浓度反应的方式减弱了炎症因子的表达。E2 还抑制了 LPS 刺激的 p38 MAPK 和 NF-κB p65 的磷酸化，但并未降低 JNK 和 ERK 1/2 的磷酸化。细胞内雌激素拮抗剂的参与部分拮抗了这种减弱作用，而 G 蛋白偶联雌激素受体激动剂的参与增强了非基因组细胞调节。这些结果表明，E2 对 LPS 诱导的绵羊输卵管上皮细胞炎症具有抑制作用，这种作用是通过雌激素受体的下游调节作用介导的。
