Work

A20 Attenuates Inflammatory Injury in Bovine Endometrial Epithelial Cells Through Autophagy-Mediated NLRP3 Inflammasome Inactivation

Year: 2025

Type: article

Abstract: Endometritis, an inflammatory disease of the uterine endometrial tissue, is a major reproductive disorder in dairy cattle that causes extensive damage to endometrial epithelial cells. Excessive activation of the NLRP3 inflammasome is strongly associated with inflammatory pathology. Autophagy plays a critical role in clearing damaged proteins, organelles, and intracellular pathogens. Additionally, the zinc finger protein A20 exhibits potent anti-inflammatory effects across various inflammatory conditions. However, the roles of A20 and autophagy in regulating the NLRP3 inflammasome in BEECs remain poorly defined. This study shows that LPS significantly increased IL-1β expression, Caspase-1 activity, and lactate dehydrogenase (LDH) levels, while inducing numerous vesicular protrusions and membrane pores, resulting in severe inflammatory injury. A20 overexpression mitigated LPS-induced NLRP3 inflammasome activation and alleviated inflammatory injury. Conversely, autophagy inhibition or A20 silencing intensified LPS-induced NLRP3 inflammasome activation and inflammatory injury. Further analysis revealed that A20 promotes autophagy, and its inhibitory effect on the NLRP3 inflammasome was diminished when autophagy was suppressed. In conclusion, A20 reduces LPS-induced inflammatory injury in BEECs by enhancing autophagy and suppressing NLRP3 inflammasome activation. These results uncover a novel regulatory role for A20 in controlling excessive NLRP3 inflammasome activation in BEECs, suggesting its potential as a therapeutic target for bovine endometritis.

Source: Animals

DOI: 10.3390/ani15243513