UFL1 modulates NLRP3 inflammasome activation and protects against pyroptosis in LPS-stimulated bovine mammary epithelial cells

摘要

UFL1 was identified as a key regulator of cellular stress, which was found to possess anti-inflammatory and cytoprotection effect in LPS-stimulated bovine mammary epithelial cells in our previous study. The NLRP3 inflammasome, which responds to various pathogenic microorganisms and sterile stressors, is involved in multiple inflammatory diseases. However, the specific effects of UFL1 on NLRP3 inflammasome activation remain elusive. Here we investigated the role of UFL1, with a focus on NLRP3 inflammasome activation and the regulation of pyroptosis in LPS-stimulated BMECs. In this study, we observed an elevating NLRP3, Caspase-1 activation and IL-1beta, secretion in mammary tissue of cows with mastitis and LPS-stimulated BMECs, and the experimental results here demonstrated that UFL1 depletion aggravated the LPS-induced NLRP3, Caspase-1 and IL-1β expression. Overexpression of UFL1 significantly suppressed the expression of NLRP3, Caspase-1 and IL-1beta, in BMECs. In addition, the suppression of NLRP3 inflammasome activation by UFL1 was partly mediated through the regulation of NF-kappaB signaling and ROS production. Furthermore, UFL1 overexpression could alleviate NLRP3 inflammasome activation-mediated pyroptosis in LPS-stimulated BMECs. These findings indicate that UFL1 can moudulate NLRP3 inflammasome activation and serve as effective strategies to diminish cell damage in inflammatory response by targeting NLRP3 inflammasome activation.