Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0031154 (
peritonitis
)
15,372
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 Ca
2+
-dependent manner. Through binding to
GPR43
, acetate activates the G
q/11
subunit and subsequent phospholipase C-IP
3
signaling to decrease Ca
2+
mobilization. In addition, acetate activates soluble adenylyl cyclase (sAC), promotes NLRP3 inflammasome ubiquitination by PKA, and ultimately induces NLRP3 degradation through autophagy. In vivo, acetate protects mice from NLRP3 inflammasome-dependent
peritonitis
and LPS-induced endotoxemia. Collectively, our research demonstrates that acetate regulates the NLRP3 inflammasome via
GPR43
and Ca
2+
-dependent mechanisms, which reveals the mechanism of metabolite-mediated NLRP3 inflammasome attenuation and highlights acetate as a possible therapeutic strategy for NLRP3 inflammasome-related diseases.
...
PMID:Acetate attenuates inflammasome activation through GPR43-mediated Ca
2+
-dependent NLRP3 ubiquitination. 3140 66
