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Open AccessArticle

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

by Sumi Park 1,2,†, Jiha Shin 1,†, Jeongyun Bae 1, Daewon Han 1, Seok-Rae Park 2,3, Jongdae Shin 1,2, Sung Ki Lee 2,4,* and Hwan-Woo Park 1,2,*
1
Department of Cell Biology, Konyang University College of Medicine, Daejeon 35365, Korea
2
Myunggok Medical Research Institute, Konyang University College of Medicine, Daejeon 35365, Korea
3
Department of Microbiology, Konyang University College of Medicine, Daejeon 35365, Korea
4
Department of Obstetrics and Gynecology, Konyang University Hospital, Daejeon 35365, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(3), 728; https://doi.org/10.3390/cells9030728
Received: 23 January 2020 / Revised: 12 March 2020 / Accepted: 12 March 2020 / Published: 16 March 2020
(This article belongs to the Section Cell Signaling and Regulated Cell Death)
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. View Full-Text
Keywords: SIRT1; NLRP3 inflammasome; maternal inflammation; human trophoblasts; placenta; oxidative stress SIRT1; NLRP3 inflammasome; maternal inflammation; human trophoblasts; placenta; oxidative stress
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MDPI and ACS Style

Park, S.; Shin, J.; Bae, J.; Han, D.; Park, S.-R.; Shin, J.; Lee, S.K.; Park, H.-W. SIRT1 Alleviates LPS-Induced IL-1β Production by Suppressing NLRP3 Inflammasome Activation and ROS Production in Trophoblasts. Cells 2020, 9, 728.

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