Liver X receptors agonists suppress NLRP3 inflammasome activation

Yu, Shui-Xing; Chen, Wei; Hu, Xiao-Zhu; Feng, Shiyuan; Li, Kun-Yu; Shuai, Qi; Lei, Qinghua; Hu, Guiqiu; Li, Ning; Zhou, Fenghua; Ma, Cun‐Gen; Du, Cheng; Yang, Yongjun

doi:10.1016/j.cyto.2016.12.003

Cited by 20 publications

(13 citation statements)

References 42 publications

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“…ILG-mediated suppression of NLRP3 and down-regulation of caspase-1 and IL-1β activation has also been reported [ 166 ]. Similar results were reported for SFN, two liver X receptors T0901317 and GW3965, and Spirodalesol [ 167 , 168 , 169 ]. Recently, the ketone body β-hydroxybutyrate (BHB) and MCC950 were revealed to specifically inhibit inflammasome activation.…”

Section: Major Therapeutic Strategies For Hepatocarcinogenesissupporting

confidence: 86%

Molecular Targets in Hepatocarcinogenesis and Implications for Therapy

Yiang

Cheng

et al. 2018

JCM

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Hepatocarcinogenesis comprises of multiple, complex steps that occur after liver injury and usually involve several pathways, including telomere dysfunction, cell cycle, WNT/β-catenin signaling, oxidative stress and mitochondria dysfunction, autophagy, apoptosis, and AKT/mTOR signaling. Following liver injury, gene mutations, accumulation of oxidative stress, and local inflammation lead to cell proliferation, differentiation, apoptosis, and necrosis. The persistence of this vicious cycle in turn leads to further gene mutation and dysregulation of pro- and anti-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-10, IL-12, IL-13, IL-18, and transforming growth factor (TGF)-β, resulting in immune escape by means of the NF-κB and inflammasome signaling pathways. In this review, we summarize studies focusing on the roles of hepatocarcinogenesis and the immune system in liver cancer. In addition, we furnish an overview of recent basic and clinical studies to provide a strong foundation to develop novel anti-carcinogenesis targets for further treatment interventions.

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Section: Major Therapeutic Strategies For Hepatocarcinogenesissupporting

confidence: 86%

Molecular Targets in Hepatocarcinogenesis and Implications for Therapy

Yiang

Cheng

et al. 2018

JCM

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“…However, under certain conditions, when “inflammatory machinery” is not properly orchestrated, inflammation may lead to significant pathology. The pathogenic role of inflammasome in many types of liver disease is well documented [141,142]. For instance, the NLRP3 inflammasomes, activated by telomere-independent repressor activator protein 1 (RAP1)/keratinocyte chemoattractant axis, played a critical role in initiating inflammation during the early stage of liver graft injury.…”

Section: Relevance Of Inflammasome In Hepatic Ischemia-reperfusionmentioning

confidence: 99%

Inflammasome-Mediated Inflammation in Liver Ischemia-Reperfusion Injury

Jiménez‐Castro

Cornide‐Petronio

Gracia‐Sancho

et al. 2019

Cells

173

138

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Ischemia-reperfusion injury is an important cause of liver damage occurring during surgical procedures including hepatic resection and liver transplantation, and represents the main underlying cause of graft dysfunction and liver failure post-transplantation. To date, ischemia-reperfusion injury is an unsolved problem in clinical practice. In this context, inflammasome activation, recently described during ischemia-reperfusion injury, might be a potential therapeutic target to mitigate the clinical problems associated with liver transplantation and hepatic resections. The present review aims to summarize the current knowledge in inflammasome-mediated inflammation, describing the experimental models used to understand the molecular mechanisms of inflammasome in liver ischemia-reperfusion injury. In addition, a clear distinction between steatotic and non-steatotic livers and between warm and cold ischemia-reperfusion injury will be discussed. Finally, the most updated therapeutic strategies, as well as some of the scientific controversies in the field will be described. Such information may be useful to guide the design of better experimental models, as well as the effective therapeutic strategies in liver surgery and transplantation that can succeed in achieving its clinical application.

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“…Furthermore, two liver X receptors T0901317 and GW3965 were identified to potently inhibit NLRP3 inflammasome activation, which was accomplished by the reduction of inflammasome-associated mtROS production, ASC oligomerization, casp1 cleavage, and IL-1β secretion. Additionally, these agonists suppressed the priming signaling of NLRP3 inflammasome activation ( 65 ). Besides, a unique mode of action in inhibiting NLRP3 inflammasome activation was recently described by Zhang et al, who found that spirodalesol repressed NLRP3 inflammasome assembly, while displayed neither inhibition of p65 activation and luciferase activity of NF-κB nor IL-1β mRNA levels in BMDMs, suggesting that spirodalesol selectively blocked signal II but not signal I of NLRP3 inflammasome activation ( 66 ).…”

Section: Pharmacological Inhibitors Of the Nlrp3 Inflammasomementioning

confidence: 99%

Relevance of the NLRP3 Inflammasome in the Pathogenesis of Chronic Liver Disease

et al. 2017

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Inflammation is a common characteristic of chronic liver disease (CLD). Inflammasomes are multiprotein complexes that can sense and recognize various exogenous and endogenous danger signals, eventually activating interleukin (IL)-1β and IL-18. The sensor component of the inflammasome system is a nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). The NLRs family pyrin domain containing 3 (NLRP3) inflammasome has been involved in the initiation and progression of CLD. However, the molecular mechanisms by which it triggers liver inflammation and damage remain unclear. Here, we focus on recent advances on the potential role of NLRP3 inflammasome activation in the progression of CLD, including viral hepatitis, non-alcoholic steatohepatitis and alcoholic liver disease, and in particular, its ability to alleviate liver inflammation in animal models. Additionally, we also discuss various pharmacological inhibitors identifying the NLRP3 inflammasome signaling cascade as novel therapeutic targets in the treatment of CLD. In summary, this review summarizes the relevance of the NLRP3 inflammasome in the initiation and progression of CLD, and provides critical targets to suppress the development of CLD in clinical management.

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Liver X receptors agonists suppress NLRP3 inflammasome activation

Cited by 20 publications

References 42 publications

Molecular Targets in Hepatocarcinogenesis and Implications for Therapy

Molecular Targets in Hepatocarcinogenesis and Implications for Therapy

Inflammasome-Mediated Inflammation in Liver Ischemia-Reperfusion Injury

Relevance of the NLRP3 Inflammasome in the Pathogenesis of Chronic Liver Disease

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