The TWIK2 Potassium Efflux Channel in Macrophages Mediates NLRP3 Inflammasome-Induced Inflammation.

ABSTRACT: Potassium (K⁺) efflux across the plasma membrane is thought to be an essential mechanism for ATP-induced NLRP3 inflammasome activation, yet the identity of the efflux channel has remained elusive. Here we identified the two-pore domain K⁺ channel (K_2P) TWIK2 as the K⁺ efflux channel triggering NLRP3 inflammasome activation. Deletion of Kcnk6 (encoding TWIK2) prevented NLRP3 activation in macrophages and suppressed sepsis-induced lung inflammation. Adoptive transfer of Kcnk6^-/- macrophages into mouse airways after macrophage depletion also prevented inflammatory lung injury. The K⁺ efflux channel TWIK2 in macrophages has a fundamental role in activating the NLRP3 inflammasome and consequently mediates inflammation, pointing t

SUBMITTER: Di A 

PROVIDER: S-EPMC6051907 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature