Acetate attenuates inflammasome activation through GPR43-mediated Ca²⁺-dependent NLRP3 ubiquitination.

ABSTRACT: Acetate has been indicated to be elevated and to regulate inflammation in inflammatory and metabolic diseases. The inflammasome serves as a key component of immune homeostasis, and its dysregulation can lead to various inflammatory disorders. However, little is known about the effects of acetate on inflammasome activation and the underlying mechanism. Here, we demonstrate that acetate attenuates inflammasome activation via GPR43 in a Ca²⁺-dependent manner. Through binding to GPR43, acetate activates the G_q/11 subunit and subsequent phospholipase C-IP₃ signaling to decrease Ca²⁺ mobilization. In addition, acetate activates soluble adenylyl cyclase (sAC), promotes NLRP3 inflammasome ubiquitination by PKA, and ultimately induces NLRP3 degradation th

SUBMITTER: Xu M 

PROVIDER: S-EPMC6802670 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature