College of Animal Science, Tarim University, Alar, Xinjiang, 843300, People's Republic of China.
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
Inflammation. 2021 Aug;44(4):1478-1489. doi: 10.1007/s10753-021-01433-y. Epub 2021 Feb 18.
Endometritis is a common inflammatory disease in uterine tissues that leads to animal infertility. Among the causes, Escherichia coli infection is one of the main reasons. Interferon-tau (IFN-τ) is the initial pregnancy signal for ruminant embryos and can induce immune tolerance in humans and other species. However, there are scarce reports on whether IFN-τ has a regulatory effect on endometrial inflammatory damage through HMGB1-NF-κB signalling. The purpose of this study was to investigate the regulatory mechanism of IFN-τ in HMGB1-NF-κB signalling in LPS-induced endometritis. ELISA and qPCR were used to detect the expression of LPS-induced pro-inflammatory cytokines in bovine endometrial epithelial cells (bEECs or BEND) under IFN-τ intervention, and the levels of HMGB1, p-IKK and p-p65 were detected by Western blotting. The nuclear translocation of NF-κB p65 was determined through immunofluorescence. In addition, bEECs were transfected with si-HMGB1 to elucidate the key role of HMGB1 and IFN-τ in the endometrial inflammatory cascade. The results indicated that IFN-τ inhibits the expression of related pro-inflammatory cytokines in an inflammatory injury model of bovine endometrial epithelial cells induced by LPS. Furthermore, experiments have proven that IFN-τ has protective effects on E. coli endotoxin-induced endometritis in mice in vivo. IFN-τ inhibited the HMGB1-NF-κB axis and significantly reduced the secretion of pro-inflammatory cytokines, the expression of HMGB1 protein and the levels of IKK and NF-κB p65 phosphorylation. In summary, our results showed that IFN-τ resists E. coli endotoxin-induced endometritis by attenuating HMGB1/NF-κB signalling.
子宫内膜炎是一种常见的子宫组织炎症性疾病，可导致动物不孕。在病因中，大肠杆菌感染是主要原因之一。干扰素-τ（IFN-τ）是反刍动物胚胎的初始妊娠信号，可诱导人和其他物种的免疫耐受。然而，关于 IFN-τ 是否通过 HMGB1-NF-κB 信号通路对子宫内膜炎症损伤具有调节作用的报道很少。本研究旨在探讨 IFN-τ 在 LPS 诱导的子宫内膜炎中对 HMGB1-NF-κB 信号通路的调节机制。采用 ELISA 和 qPCR 检测 IFN-τ 干预下 LPS 诱导的牛子宫内膜上皮细胞（bEEC 或 BEND）中促炎细胞因子的表达，Western blot 检测 HMGB1、p-IKK 和 p-p65 的水平，免疫荧光检测 NF-κB p65 的核转位。此外，通过 si-HMGB1 转染 bEECs，阐明 HMGB1 和 IFN-τ 在子宫内膜炎症级联反应中的关键作用。结果表明，IFN-τ 抑制 LPS 诱导的牛子宫内膜上皮细胞炎症损伤模型中相关促炎细胞因子的表达。此外，实验证明 IFN-τ 在体内对大肠杆菌内毒素诱导的小鼠子宫内膜炎具有保护作用。IFN-τ 抑制 HMGB1-NF-κB 轴，显著减少促炎细胞因子的分泌、HMGB1 蛋白的表达以及 IKK 和 NF-κB p65 磷酸化水平。综上所述，我们的研究结果表明，IFN-τ 通过减弱 HMGB1/NF-κB 信号通路来抵抗大肠杆菌内毒素诱导的子宫内膜炎。
