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

Abstract

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.

Nutraceutical Strategies for Suppressing NLRP3 Inflammasome Activation: Pertinence to the Management of COVID-19 and Beyond

“…There is also some evidence that, at least in certain contexts, AMPK can accelerate the proteasomal degradation of TXNIP. AMPK activation may also oppose inflammasome activation via activation of the deacetylase Sirt1, which has been shown to inhibit inflammasome assembly in several types of cells [ 135 , 136 , 137 , 138 , 139 , 140 , 141 ]. Sirt1 activity could be expected to inhibit inflammasome priming by suppressing the transcriptional activity of NF-kappaB, but additional mechanisms may be at play [ 142 , 143 ].…”

Expression Regulation and Physiological Role of Transcription Factor FOXO3a During Ovarian Follicular Development

“…Under oxidative stress, accumulated reactive oxygen species (ROS) leads to post-translational modifications of FOXO3a, thereby regulating the activity and function of FOXO3a. Park et al (2020) demonstrated that SIRT1 can downregulate ROS and form a complex with FOXO3a in cells, which can improve the ability of FOXO3a to induce cell cycle arrest and promote cell survival. Recent findings have indicated that resveratrol, a plant polyphenolic compound, can enhance SIRT1 and decrease ovarian oxidative stress as well as inhibit phosphorylation of p66Shc, both in vivo and in vitro (Wang et al, 2020).…”

Activating Nrf2 signalling alleviates osteoarthritis development by inhibiting inflammasome activation

“…6 As one of inflammasomes, nod-like receptor pyrin domain 3 (NLRP3) is a protein complex composed of NLRP3, apoptosis-associated speck-like protein(ASC) and caspase-1 that can be activated by lipopolysaccharide (LPS), which is responsible for regulating inflammatory response. [7][8][9] Then, the activation of inflammasome can activate and cleave caspase-1 to trigger the maturation and secretion of IL-1β and IL-18, thus regulating inflammation. 10 Particularly, it has been shown that NLRP3 exerts an inflammatory role in the development of OA.…”