Squaramides enhance NLRP3 inflammasome activation by lowering intracellular potassium.

ABSTRACT: The NLRP3 inflammasome is a component of the inflammatory response to infection and injury, orchestrating the maturation and release of the pro-inflammatory cytokines interleukin-1β (IL-1β), IL-18, and triggering pyroptotic cell death. Appropriate levels of NLRP3 activation are needed to avoid excessive tissue damage while ensuring host protection. Here we report a role for symmetrical diarylsquaramides as selective K⁺ efflux-dependent NLRP3 inflammasome enhancers. Treatment of macrophages with squaramides potentiated IL-1β secretion and ASC speck formation in response to K⁺ efflux-dependent NLRP3 inflammasome activators without affecting priming, endosome cargo trafficking, or activation of other inflammasomes. The squaramides lowered intracellular K⁺ conc

SUBMITTER: Seoane PI 

PROVIDER: S-EPMC10739973 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature