Browsing by Subject "Chloride"
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- PublicationOpen AccessChloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming(National Academy of Sciences, 2018-09-19) Martín Sánchez, María Rosario Fátima; Pelegrín Vivancos, Pablo; Green, Jack Peter; Yu, Shi; Lopez-Castejon, Gloria; Lawrence, Catherine B.; Brough, David; FarmacologíaThe NLRP3 inflammasome is an important regulator of inflammation and immunity. It is a multi-molecular platform formed within cells that facilitates the activation of pro-inflammatory caspases to drive secretion of cytokines such as IL-1β. Knowledge of the mechanisms regulating formation of the NLRP3-inflammasome is incomplete. Here we report Cl- channel dependent formation of dynamic ASC oligomers and inflammasome specks that remain inactive in the absence of K+ efflux. Formed after Cl- efflux exclusively ASC specks are NLRP3 dependent, reversible, and inactive, though they further prime inflammatory responses accelerating and enhancing release of IL-1β in response to a K+ efflux inducing stimulus. NEK7 is a specific K+ sensor and does not associate with NLRP3 under conditions stimulating exclusively Cl- efflux, but does after K+ efflux, activating the complex driving inflammation. Our investigation delivers new mechanistic understanding into inflammasome activation and the regulation of inflammatory responses.