LRRC8A is essential for hypotonicity-, but not for DAMP-induced NLRP3 inflammasome activation.

ABSTRACT: The NLRP3 inflammasome is a multi-molecular protein complex that converts inactive cytokine precursors into active forms of IL-1β and IL-18. The NLRP3 inflammasome is frequently associated with the damaging inflammation of non-communicable disease states and is considered an attractive therapeutic target. However, there is much regarding the mechanism of NLRP3 activation that remains unknown. Chloride efflux is suggested as an important step in NLRP3 activation, but which chloride channels are involved is still unknown. We used chemical, biochemical, and genetic approaches to establish the importance of chloride channels in the regulation of NLRP3 in murine macrophages. Specifically, we identify LRRC8A, an essential component of volume-regulated anion channels (VRAC), as a vital regulator

SUBMITTER: Green JP 

PROVIDER: S-EPMC7679132 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature