MiR‐223‐3p inhibits rTp17‐induced inflammasome activation and pyroptosis by targeting NLRP3

Long, Fu‐Quan; Kou, Caixia; Li, Ké; Wu, Juan; Wang, Qianqiu

doi:10.1111/jcmm.16061

Cited by 53 publications

(49 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Huang et al found that H 2 S suppressed HG-induced cardiomyocyte inflammation and apoptosis by inhibiting the TLR4/NF-κB pathway and its downstream NLRP3 inflammasome activation [26]. Studies from other group also revealed DM-induced arrhythmias could be successfully treated by inhibiting the IL-1β axis with either IL-1 receptor antagonist or by inhibiting the NLRP3 inflammasome [27,28]. In fact, different concentrations of H 2 O 2 have different Reactive oxygen species (ROS) serves as important inflammation activating signals.…”

Section: Discussionmentioning

confidence: 99%

MiR‐599 Protects Cardiomyocytes against Oxidative Stress‐Induced Pyroptosis

Fan

Zhan

Yao

et al. 2021

BioMed Research International

View full text Add to dashboard Cite

Oxidative stress is a crucial factor and key promoter of a variety of cardiovascular diseases associated with cardiomyocyte injury. Emerging literatures suggest that pyroptosis plays a key role in cardiac damages. However, whether pyroptosis contributes to cardiomyocyte injury under oxidative stress and the underlying molecular mechanisms are totally unclear. This study was designed to investigate the potential role of pyroptosis in H2O2-induced cardiomyocyte injury and to elucidate the potential mechanisms. Primary cardiomyocytes from neonatal Wistar rats were utilized. These myocytes were treated with different concentrations of H2O2 (25, 50, and 100 μM) for 24 h to induce oxidative injury. Our results indicated that mRNA and protein levels of ASC were remarkably upregulated and caspase-1 was activated. Moreover, the expressions of inflammatory factors IL-1β and IL-18 were also increased. Luciferase assay showed that miR-599 inhibited ASC expression through complementary binding with its 3 ′ UTR. MiR-599 expression was substantially reduced in H2O2-treated cardiomyocytes. Upregulation of miR-599 inhibited cardiomyocyte pyroptosis under oxidative stress, and opposite results were found by decreasing the expression of miR-599. Consistently, miR-599 overexpression ameliorated cardiomyocyte injury caused by H2O2. Therefore, miR-599 could be a promising therapeutic approach for the management of cardiac injury under oxidative condition.

show abstract

Section: Discussionmentioning

confidence: 99%

MiR‐599 Protects Cardiomyocytes against Oxidative Stress‐Induced Pyroptosis

Fan

Zhan

Yao

et al. 2021

BioMed Research International

View full text Add to dashboard Cite

show abstract

Section: The Roles Of Ncrnas In Inflammasomes Activation In Inflammatory Diseasesmentioning

confidence: 99%

“…67 Moreover, a study involving Treponema pallidum subspecies pallidum (T pallidum) infection showed that a dramatic reduction in the serum levels of miR-223-3p of patients with syphilis compared with healthy controls, which could target NLRP3 to suppress inflammasome activation and pyroptosis in T pallidum-induced Human Umbilical Vein Endothelial Cells (HUVECs), thus indicating a potential target for syphilis-induced endothelial injury. 68 Apart from targeting NLRP3 directly, ncRNAs can also regulate the NLRP3 inflammasome activation process. The NLRP3 inflammasome can be activated by a diverse range of stimuli and a 2-signal model has been proposed for to explain this process (Figure 3).…”

Section: The Roles Of Ncrnas In Regulating Inflammasomes Activation In Different Types Of Microbial Infectionmentioning

confidence: 99%

Non-Coding RNAs: Master Regulators of Inflammasomes in Inflammatory Diseases

Wang¹,

Yang²,

Yang³

et al. 2021

JIR

View full text Add to dashboard Cite

Emerging data indicates that non-coding RNAs (ncRNAs) represent more than just “junk sequences” of the genome and have been found to be involved in multiple diseases by regulating various biological process, including the activation of inflammasomes. As an important aspect of innate immunity, inflammasomes are large immune multiprotein complexes that tightly regulate the production of pro-inflammatory cytokines and mediate pyroptosis; the activation of the inflammasomes is a vital biological process in inflammatory diseases. Recent studies have emphasized the function of ncRNAs in the fine control of inflammasomes activation either by directly targeting components of the inflammasomes or by controlling the activity of various factors that control the activation of inflammasomes; consequently, ncRNAs may represent potential therapeutic targets for inflammatory diseases. Understanding the precise role of ncRNAs in controlling the activation of inflammasomes will help us to design targeted therapies for multiple inflammatory diseases. In this review, we summarize the regulatory role and therapeutic potential of ncRNAs in the activation of inflammasomes by focusing on a range of inflammatory diseases, including microbial infection, sterile inflammatory diseases, and fibrosis-related diseases. Our goal is to provide new ideas and perspectives for future research.

show abstract

“…Previously, it was found that NLRP3 is one of the target genes of miR-223 (Bauernfeind et al, 2012). Recent studies have confirmed that miR-223 can inhibit inflammation by targeting NLRP3, thereby suppressing inflammasome activation and pyroptosis in T palliduminfected endothelial cells (Long et al, 2020), limiting inflammation in human dental pulp fibroblasts (Wang et al, 2020), relieving spinal cord injury (Zhang et al, 2020), and modulating dendritic cell function to ameliorates autoimmune myocarditis (Zhou et al, 2017). However, the status of miR-223 expression and the potential role of miR-223 in gout have not been reported.…”

Section: Introductionmentioning

confidence: 96%

“…MicroRNAs (miRs) are short non-coding RNAs with a length of approximately 22 nucleotides. Recently, the role of miRs in negatively regulating inflammation in autoimmune diseases and inflammation disorders has received increasing attention (Henshall et al, 2016;Long et al, 2020). miR-223 is expressed in myeloid cells, and miR-223 under-expression is associated with many diseases, including leukemia, hepatitis B, influenza, lymphoma, and inflammation (Gilicze et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-223 Suppresses IL-1β and TNF-α Production in Gouty Inflammation by Targeting the NLRP3 Inflammasome

et al. 2021

View full text Add to dashboard Cite

Introduction: MicroRNA-223 (MiR-223) serves as an important regulator of inflammatory and immune responses and is implicated in several auto-inflammatory disorders. Here, we measured miR-223 expression in acute and intercritical gout patients, after which we used RAW264.7 macrophages transfected with a miR-223 mimic/inhibitor to determine the function of miR-223 in monosodium urate (MSU)-induced gouty inflammation.Methods and Results: MiR-223 was detected among 122 acute gout patients (AG), 118 intercritical gout patients (IG), and 125 healthy subjects (HC). RAW264.7 macrophages were cultured and treated with MSU. Over-expression or under-expression of miR-223 was inducted in RAW264.7 macrophages to investigate the function of miR-223. Real-time quantitative PCR, ELISA and western blotting were used to determine the expression levels of miR-223, cytokines and the NLRP3 inflammasome (NLRP3, ASC, and caspase-1). MiR-223 expression was significantly decreased in the AG group in comparison with the IG and HC groups (p < 0.001, respectively). Up-regulated expression of miR-223 was observed after acute gout remission in comparison with that observed during gout flares in 30 paired cases (p < 0.001). The abundance of the NLRP3 inflammasome and cytokines was significantly increased after RAW264.7 macrophages were treated with MSU (p < 0.01, respectively), while that of miR-223 was significantly reduced (p < 0.01). Up-regulation of miR-223 decreased the concentrations of IL-1β and TNF-α, as well as the NLRP3 inflammasome expression (p < 0.01, respectively), while IL-37 and TGF-β1 levels were unchanged (p > 0.05, respectively). Under-expression of miR-223 increased the concentrations of IL-1β and TNF-α, as well as NLRP3 inflammasome expression (p < 0.01, respectively), while IL-37 and TGF-β1 levels were not influenced (p > 0.05, respectively).Conclusion: These findings suggest that miR-223 provides negative feedback regulation of the development of gouty inflammation by suppressing production of IL-1β and TNF-α, but not by regulating IL-37 and TGF-β1. Moreover, miR-223 regulates cytokine production by targeting the NLRP3 inflammasome.

show abstract

MiR‐223‐3p inhibits rTp17‐induced inflammasome activation and pyroptosis by targeting NLRP3

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 53 publications

References 35 publications

MiR‐599 Protects Cardiomyocytes against Oxidative Stress‐Induced Pyroptosis

MiR‐599 Protects Cardiomyocytes against Oxidative Stress‐Induced Pyroptosis

Non-Coding RNAs: Master Regulators of Inflammasomes in Inflammatory Diseases

MicroRNA-223 Suppresses IL-1β and TNF-α Production in Gouty Inflammation by Targeting the NLRP3 Inflammasome

Contact Info

Product

Resources

About