Oridonin attenuates liver ischemia-reperfusion injury by suppressing PKM2/NLRP3-mediated macrophage pyroptosis.
Cell Immunol
; 401-402: 104838, 2024.
Article
en En
| MEDLINE
| ID: mdl-38810591
ABSTRACT
BACKGROUND:
The NOD-like receptor protein 3 (NLRP3) mediated pyroptosis of macrophages is closely associated with liver ischemia reperfusion injury (IRI). As a covalent inhibitor of NLRP3, Oridonin (Ori), has strong anti-inflammasome effect, but its effect and mechanisms for liver IRI are still unknown.METHODS:
Mice and liver macrophages were treated with Ori, respectively. Co-IP and LC-MS/MS analysis of the interaction between PKM2 and NLRP3 in macrophages. Liver damage was detected using H&E staining. Pyroptosis was detected by WB, TEM, and ELISA.RESULTS:
Ori ameliorated liver macrophage pyroptosis and liver IRI. Mechanistically, Ori inhibited the interaction between pyruvate kinase M2 isoform (PKM2) and NLRP3 in hypoxia/reoxygenationï¼H/Rï¼-induced macrophages, while the inhibition of PKM2/NLRP3 reduced liver macrophage pyroptosis and liver IRI.CONCLUSION:
Ori exerted protective effects on liver IRI via suppressing PKM2/NLRP3-mediated liver macrophage pyroptosis, which might become a potential therapeutic target in the clinic.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión
/
Diterpenos de Tipo Kaurano
/
Piroptosis
/
Proteína con Dominio Pirina 3 de la Familia NLR
/
Hígado
/
Macrófagos
/
Ratones Endogámicos C57BL
Límite:
Animals
Idioma:
En
Revista:
Cell Immunol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China