ATP exposure stimulates glutathione efflux as a necessary switch for NLRP3 inflammasome activation

• DOI: 10.1016/j.redox.2021.101930
• Publication Date: 2021-03-11T08:18:16Z
• Authors: Tianli Zhang; Hiroyasu Tsutsuki; Waliul Islam; Katsuhiko Ono; Kohsuke Takeda; Takaaki Akaike; Tomohiro Sawa
• Keywords: Efflux; Proinflammatory cytokine

The NLRP3 inflammasome is a multiprotein complex responsible for the maturation of precursor forms interleukin (IL)-1β and IL-18 into active proinflammatory cytokines. Increasing evidence suggests that modulation redox homeostasis contributes to activation inflammasome. However, specific mechanistic details remain unclear. We demonstrate here ATP exposure evoked sharp decrease in glutathione (GSH) levels macrophages, which led activation. detected an increase GSH culture supernatants was comparable stimulated efflux. Exogenous addition P2X7 receptor antagonist, GSH, or oxidized form GSSG attenuated this Also, exogenous strongly inhibited vitro vivo. These data suggest efflux controls activation, may lead development novel therapeutic strategies inflammasome-associated disorders.