Dong Junsheng, Ji Bowen, Jiang Yeqi, Fei Fan, Guo Long, Liu Kangjun, Cui Luying, Meng Xia, Li Jianji, Wang Heng
College of Veterinary Medicine, Yangzhou University, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou 225009, China.
Animals (Basel). 2024 Oct 6;14(19):2876. doi: 10.3390/ani14192876.
Endometritis represents a prevalent condition in perinatal dairy cows. Bovine endometrial epithelial cells (BEECs), as the primary interface between cavity and the external environment, are particularly vulnerable to infection by pathogenic bacteria following parturition. A20 is essential for regulating inflammation and modulating immune responses. Nevertheless, the exact role of A20 in the BEECs in response to inflammatory response is not fully understood. An endometritis model infected by () in vivo and a BEECs inflammation model induced with lipopolysaccharide (LPS) in vitro were built to investigate the function and governing mechanisms of A20 in endometritis. The results showed that infection with resulted in endometrial damage, inflammatory cell infiltration, and upregulation of inflammatory factors in dairy cows. Furthermore, A20 expression was upregulated in the endometrium of cows with endometritis and in BEECs following LPS stimulation. A20 overexpression attenuated the level of proinflammatory cytokines in LPS-stimulated BEECs; conversely, A20 knockdown lead to an exacerbated response to LPS stimulation. The overexpression of A20 was shown to activate autophagy and suppress the NF-κB signaling pathway in LPS-stimulated BEECs. However, blocking autophagy with chloroquine notably attenuated the anti-inflammatory effect of A20, leading to the activation of the NF-κB signaling pathway. In summary, the study demonstrated that A20's suppression of inflammation in LPS-stimulated BEECs is associated with the activation of autophagy. Therefore, the A20 protein showed potential as a novel treatment focus for managing endometritis in dairy cows.
子宫内膜炎是围产期奶牛的一种常见病症。牛子宫内膜上皮细胞（BEECs）作为子宫腔与外部环境之间的主要界面，在分娩后特别容易受到病原菌感染。A20对于调节炎症和调控免疫反应至关重要。然而，A20在BEECs中对炎症反应的确切作用尚未完全明确。本研究构建了体内由（）感染的子宫内膜炎模型以及体外由脂多糖（LPS）诱导的BEECs炎症模型，以探究A20在子宫内膜炎中的功能及其调控机制。结果表明，（）感染导致奶牛子宫内膜损伤、炎性细胞浸润以及炎性因子上调。此外，在患子宫内膜炎奶牛的子宫内膜以及LPS刺激后的BEECs中，A20表达上调。A20过表达可降低LPS刺激的BEECs中促炎细胞因子水平；相反，A20基因敲低导致对LPS刺激的反应加剧。A20过表达可激活LPS刺激的BEECs中的自噬并抑制NF-κB信号通路。然而，用氯喹阻断自噬显著减弱了A20的抗炎作用，导致NF-κB信号通路激活。总之，该研究表明A20对LPS刺激的BEECs炎症的抑制作用与自噬激活有关。因此，A20蛋白有望成为治疗奶牛子宫内膜炎的新靶点。
