Autophagy Mediates Escherichia Coli -Induced Cellular Inflammatory Injury by Regulating Calcium Mobilization, Mitochondrial Dysfunction, and Endoplasmic Reticulum Stress

• Published in: International journal of molecular sciences Vol. 23; no. 22; p. 14174
• Main Authors: Liu, Jianguo, Qiu, Rendong, Liu, Ran, Song, Pengjie, Lin, Pengfei, Chen, Huatao, Zhou, Dong, Wang, Aihua, Jin, Yaping
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.11.2022; MDPI
• Subjects: Animals; Autophagy; Autophagy - physiology; Bacterial infections; Biosynthesis; Calcium (extracellular); Calcium (mitochondrial); Calcium - metabolism; Calcium imaging; Calcium ions; Calcium mobilization; Cattle; Chains; Cytochrome; Cytochrome c; Cytokines; DNA biosynthesis; E coli; Electron transport; Endometritis; Endometritis - pathology; Endometrium; Endoplasmic reticulum; endoplasmic reticulum stress; Endoplasmic Reticulum Stress - physiology; Epithelial cells; Epithelium; Escherichia coli; Escherichia coli Infections - complications; Female; Gene expression; Homeostasis; IL-1β; Infections; Inflammasomes; Inflammation; Inflammation - metabolism; Inflammatory response; Interleukin 18; Metabolism; Mitochondria; Mitochondria - pathology; Mitochondrial DNA; mitochondrial dysfunction; NF-κB protein; Proteins; Reproductive disorders; Uterus; endometritis; mitochondrial dysfunction; autophagy; calcium mobilization; inflammation; endoplasmic reticulum stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232214174

Bovine endometritis is a reproductive disorder that is induced by mucus or purulent inflammation of the uterine mucosa. However, the intracellular control chain during inflammatory injury remains unclear. In the present study, we found that activated the inflammatory response through the assembly of the NLRP3 inflammasome and activation of the NF-κB p65 subunit in primary bovine endometrial epithelial cells (bEECs). Infection with also led to an abnormal increase in cytoplasmic calcium and mitochondrial dysfunction. Additionally, live-cell imaging of calcium reporters indicated that the increase in cytosolic calcium mainly was caused by the release of Ca ions stored in the ER and mitochondria, which was independent of extracellular calcium. Cytoplasmic calcium regulates mitochondrial respiratory chain transmission, DNA replication, and biogenesis. Pretreatment with NAC, BAPTA-AM, or 2-APB reduced the expression of IL-1β and IL-18. Moreover, ERS was involved in the regulation of bovine endometritis and cytosolic calcium was an important factor for regulating ERS in -induced inflammation. Finally, activation of autophagy inhibited the release of IL-1β and IL-18, cytochrome c, ATP, ERS-related proteins, and cytoplasmic calcium. Collectively, our findings demonstrate that autophagy mediated -induced cellular inflammatory injury by regulating cytoplasmic calcium, mitochondrial dysfunction, and ERS.