SIRT1 Alleviates LPS-Induced IL-1β Production by Suppressing NLRP3 Inflammasome Activation and ROS Production in Trophoblasts

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 3; p. 728
• Main Authors: Park, Sumi, Shin, Jiha, Bae, Jeongyun, Han, Daewon, Park, Seok-Rae, Shin, Jongdae, Lee, Sung Ki, Park, Hwan-Woo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.03.2020; MDPI
• Subjects: Animals; Female; Histone deacetylase; human trophoblasts; Humans; IL-1β; Immunoglobulins; Inflammasomes; Inflammasomes - metabolism; Inflammation; Interleukin-1beta - biosynthesis; Laboratory animals; Lipopolysaccharides; Lipopolysaccharides - pharmacology; maternal inflammation; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; nlrp3 inflammasome; Oxidative stress; Penicillin; Placenta; Plasmids; Pre-eclampsia; Pregnancy; Pregnancy complications; Premature birth; Premature Birth - metabolism; Proteins; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; sirt1; SIRT1 protein; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Therapeutic applications; Trophoblasts; Trophoblasts - metabolism; Tumor necrosis factor-TNF; St Louis Missouri; United States > US; placenta; NLRP3 inflammasome; maternal inflammation; SIRT1; human trophoblasts; oxidative stress
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9030728

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)-1β secretion. Furthermore, knockdown of NLRP3 considerably attenuated the increase of IL-1β 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.