Posttreatment of Maresin1 Inhibits NLRP3 inflammasome activation via promotion of NLRP3 ubiquitination

Zheng, Simin; Ma, Minqi; Li, Zhong-wang; Yu, Hao; Fu, Panhan; Jin, Shudong

doi:10.1096/fj.202000665rr

Cited by 21 publications

(8 citation statements)

References 42 publications

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“…105 Activation of the cAMP-PKA signaling pathway is linked to inhibition of NLRP3 inflammasome activity through enhancement of K63-linked ubiquitination of NLRP3. 233 Genistein-mediated anti-inflammasome activity is mediated through TGF5-cAMP signaling via increased intracellular cAMP levels 234 Foxp1 was reported to have a negative regulatory function on endothelial NLRP3 inflammasome activation, acting as a gatekeeper of vessel inflammation. 235 Endothelial Foxp1 is regulated by Krüppel-like factor 2 (Klf2) and further regulates NLRP3 inflammasome activation through direct regulation of endothelial inflammasome components, including NLRP3 and caspase-1.…”

Section: Dual Regulatory Mechanisms Controlling the Nlrp3 Inflammasomementioning

confidence: 99%

An update on the regulatory mechanisms of NLRP3 inflammasome activation

et al. 2021

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The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a multiprotein complex involved in the release of mature interleukin-1β and triggering of pyroptosis, which is of paramount importance in a variety of physiological and pathological conditions. Over the past decade, considerable advances have been made in elucidating the molecular mechanisms underlying the priming/licensing (Signal 1) and assembly (Signal 2) involved in NLRP3 inflammasome activation. Recently, a number of studies have indicated that the priming/licensing step is regulated by complicated mechanisms at both the transcriptional and posttranslational levels. In this review, we discuss the current understanding of the mechanistic details of NLRP3 inflammasome activation with a particular emphasis on protein-protein interactions, posttranslational modifications, and spatiotemporal regulation of the NLRP3 inflammasome machinery. We also present a detailed summary of multiple positive and/or negative regulatory pathways providing upstream signals that culminate in NLRP3 inflammasome complex assembly. A better understanding of the molecular mechanisms underlying NLRP3 inflammasome activation will provide opportunities for the development of methods for the prevention and treatment of NLRP3 inflammasome-related diseases.

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Section: Dual Regulatory Mechanisms Controlling the Nlrp3 Inflammasomementioning

confidence: 99%

An update on the regulatory mechanisms of NLRP3 inflammasome activation

et al. 2021

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“…Maresin1(MaR1), derived from n-3 unsaturated fatty acids, is one of the latest families of anti-inflammatory mediators. Studies have confirmed that MaR1 played a protective role in a variety of chronic inflammatory diseases by enhancing macrophage phagocytosis, reducing the production of pro-inflammatory factors and ROS, and inhibiting the nuclear factor-kappa B (NF-κB) activation ( Zhang et al, 2017 ; Wang et al, 2020a ; Zheng et al, 2020 ). ROS is a key mediator in the induction of ferroptosis, therefore MaR1 may inhibit ferroptosis by inhibiting ROS production caused by GalN/LPS.…”

Section: Introductionmentioning

confidence: 99%

Maresin1 Protect Against Ferroptosis-Induced Liver Injury Through ROS Inhibition and Nrf2/HO-1/GPX4 Activation

et al. 2022

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Drugs, viruses, and chemical poisons stimulating live in a short period of time can cause acute liver injury (ALI). ALI can further develop into serious liver diseases such as cirrhosis and liver cancer. Therefore, how to effectively prevent and treat ALI has become the focus of research. Numerous studies have reported Maresin1 (MaR1) has anti-inflammatory effect and protective functions on organs. In the present study, we used d-galactosamine/lipopolysaccharide (D-GalN/LPS) to establish an ALI model, explored the mechanism of liver cells death caused by D-GalN/LPS, and determined the effect of MaR1 on D-GalN/LPS-induced ALI. In vivo experiments, we found that MaR1 and ferrostatin-1 significantly alleviated D-GalN/LPS-induced ALI, reduced serum alanine transaminase and aspartate transaminase levels, and improved the survival rate of mice. Meanwhile, MaR1 inhibited hepatocyte death, inhibited tissue reactive oxygen species (ROS) expression, reduced malondialdehyde (MDA), reduced glutathione (GSH), GSH/oxidized glutathione (GSSG), and iron content induced by D-GalN/LPS in mice. In addition, MaR1 inhibited ferroptosis-induced liver injury through inhibiting the release of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6. Subsequently, western blot showed that MaR1 improved the expression of nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4). In vitro experiments, we found that MaR1 inhibited LPS-induced and erastin-induced cell viability reduction. Meanwhile, we found that MaR1 increased the MDA and GSH levels in cells. Western blot showed that MaR1 increased the expression level of Nrf2/HO-1/GPX4. Next, the Nrf2 was knocked down in HepG2 cells, and the results showed that the protective effect of MaR1 significantly decreased. Finally, flow cytometry revealed that MaR1 inhibited ROS production and apoptosis. Overall, our study showed MaR1 inhibited ferroptosis-induced liver injury by inhibiting ROS production and Nrf2/HO-1/GPX4 activation.

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“…In most cases, NLRP3 upregulation is responsible for amplified inflammation and other pathological effects. To date, the upregulation of NLRP3 has been attributed to its enhancement of transcription or protein stability 34 , 35 . In this study, we reported for the first time that, APA-induced enhancement of NLRP3 mRNA stability, is also a vital mechanism for NLRP3 upregulation.…”

Section: Discussionmentioning

confidence: 99%

“…Aberrant expression of NLRP3 is responsible for overactivated inflammation and subsequent onset of disease 35 , 36 . However, to date, NLRP3 upregulation is mostly found to be associated with enhancement of transcriptional activity or protein stability of NLRP3.…”

Section: Discussionmentioning

confidence: 99%

Alternative polyadenylation trans-factor FIP1 exacerbates UUO/IRI-induced kidney injury and contributes to AKI-CKD transition via ROS-NLRP3 axis

et al. 2021

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NLRP3, a decisive role in inflammation regulation, is obviously upregulated by oxidative stress in kidney injury. The NLRP3 upregulation leads to unsolved inflammation and other pathological effects, contributing to aggravation of kidney injury and even transition to chronic kidney disease (CKD). However, the mechanism for NLRP3 upregulation and further aggravation of kidney injury remains largely elusive. In this study, we found NLRP3 3′UTR was shortened in response to kidney injury in vivo and oxidative stress in vitro. Functionally, such NLRP3 3′UTR shortening upregulated NLRP3 expression and amplified inflammation, fibrogenesis, ROS production and apoptosis, depending on stabilizing NLRP3 mRNA. Mechanistically, FIP1 was found to bind to pPAS of NLRP3 mRNA via its arginine-rich domain and to induce NLRP3 3′UTR shortening. In addition, FIP1 was upregulated in CKD specimens and negatively associated with renal function of CKD patients. More importantly, we found FIP1 was upregulated by oxidative stress and required for oxidative stress-induced NLRP3 upregulation, inflammation activation, cell damage and apoptosis. Finally, we proved that FIP1 silencing attenuated the inflammation activation, fibrogenesis, ROS production and apoptosis induced by UUO or IRI. Taken together, our results demonstrated that oxidative stress-upregulated FIP1 amplified inflammation, fibrogenesis, ROS production and apoptosis via inducing 3′UTR shortening of NLRP3, highlighting the importance of crosstalk between oxidative stress and alternative polyadenylation in AKI-CKD transition, as well as the therapeutic potential of FIP1 in kidney injury treatment.

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Posttreatment of Maresin1 Inhibits NLRP3 inflammasome activation via promotion of NLRP3 ubiquitination

Cited by 21 publications

References 42 publications

An update on the regulatory mechanisms of NLRP3 inflammasome activation

An update on the regulatory mechanisms of NLRP3 inflammasome activation

Maresin1 Protect Against Ferroptosis-Induced Liver Injury Through ROS Inhibition and Nrf2/HO-1/GPX4 Activation

Alternative polyadenylation trans-factor FIP1 exacerbates UUO/IRI-induced kidney injury and contributes to AKI-CKD transition via ROS-NLRP3 axis

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