SIRT1 Alleviates LPS-Induced IL-1ß Production by Suppressing NLRP3 Inflammasome Activation and ROS Production in Trophoblasts.
Cells
; 9(3)2020 03 16.
Article
en En
| MEDLINE
| ID: mdl-32188057
Emerging evidence indicates that aberrant maternal inflammation is associated with several pregnancy-related disorders such as preeclampsia, preterm birth, and intrauterine growth restriction. Sirtuin1 (SIRT1), a class III histone deacetylase, is involved in the regulation of various physiopathological processes including cellular inflammation and metabolism. However, the effect of SIRT1 on the placental proinflammatory environment remains to be elucidated. In this study, we investigated the effect of SIRT1 on lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation and its underlying mechanisms in human first-trimester trophoblasts (Sw.71 and HTR-8/SVneo cells). Treatment with LPS elevated SIRT1 expression and induced NLRP3 inflammasome activation in mouse placental tissues and human trophoblasts. Knockdown of SIRT1 enhanced LPS-induced NLRP3 inflammasome activation, inflammatory signaling, and subsequent interleukin (IL)-1ß secretion. Furthermore, knockdown of NLRP3 considerably attenuated the increase of IL-1ß secretion in SIRT1-knockdown cells treated with LPS. Moreover, SIRT1 inhibited LPS-induced NLRP3 inflammasome activation by reducing oxidative stress. This study revealed a novel mechanism via which SIRT1 exerts anti-inflammatory effects, suggesting that SIRT1 is a potential therapeutic target for the prevention of inflammation-associated pregnancy-related complications.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trofoblastos
/
Sirtuina 1
/
Proteína con Dominio Pirina 3 de la Familia NLR
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cells
Año:
2020
Tipo del documento:
Article
Pais de publicación:
Suiza