Kynurenic acid inhibits macrophage pyroptosis by suppressing ROS production via activation of the NRF2 pathway.
Mol Med Rep
; 28(5)2023 Nov.
Article
en En
| MEDLINE
| ID: mdl-37772394
ABSTRACT
Macrophage pyroptosis and related inflammatory responses play an important role in periodontitis. Kynurenic acid (KA) is hypothesized to have antiinflammatory potential, but whether KA can inhibit macrophage pyroptosis and the underlying mechanisms remain unclear. Lipopolysaccharide (LPS) was used to induce pyroptosis in THP1derived macrophages. KA or ML385 was used to pretreat macrophages, after which, cell viability, NODlike receptor protein 3 (NLRP3) inflammasomerelated protein expression, oxidative stress levels and nuclear factor erythroid 2related factor 2 (NRF2) expression were measured. The results showed that KA improved the LPSinduced decrease in macrophage viability and lactate dehydrogenase release. KA prevented THP1 macrophage pyroptosis induced by LPS by reducing the expression of NLRP3, GasderminD, and Caspase1, and decreased the expression of inflammatory factors. KA suppressed NLRP3 inflammasome activation by inhibiting ROS overproduction and increasing Heme Oxygenase 1 and glutathione levels. Moreover, KA promoted NRF2 translocation from the cytoplasm to the nucleus. In addition, the antipyroptotic and antioxidant effects of KA were reversed by ML385 inhibition of NRF2. In the present study, it was found that KA significantly suppressed macrophage pyroptosis induced by LPS. It was further demonstrated that the antipyroptotic effects of KA were mediated by activation of the NRF2 pathway.
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Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Inflamasomas
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Proteína con Dominio Pirina 3 de la Familia NLR
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Ácido Quinurénico
Idioma:
En
Revista:
Mol Med Rep
Año:
2023
Tipo del documento:
Article