MicroRNA-20a negatively regulates expression of NLRP3-inflammasome by targeting TXNIP in adjuvant-induced arthritis fibroblast-like synoviocytes

Li, Xiaofeng; Shen, Wenwen; Sun, Ying‐Yin; Li, Wanxia; Sun, Zhenghao; Liu, Yan‐Hui; Zhang, Lei; Huang, Cheng; Meng, Xiao‐Ming; Li, Jun

doi:10.1016/j.jbspin.2015.10.007

Cited by 87 publications

(61 citation statements)

References 35 publications

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“…Caspase-1 activation induced EC dysfunction, leading to vascular remodeling and atherosclerosis [26]. Similarly, Li et al also demonstrated that miR-20a over-expression reduced the formation of the NLRP3 inflammasome, including reducing NLRP3 and caspase-1 expression [27], which possibly explains how miR-22 expression is related to NLRP3 and caspase-1 in our study.…”

Section: Discussionsupporting

confidence: 71%

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Huang

Wei

Lin

et al. 2017

Cell Physiol Biochem

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Background/Aims: This study aimed to identify the role of microRNA-22 (miR-22) in endothelial cell (EC) injury in coronary heart disease (CHD) by targeting NLRP3 through the inflammasome signaling pathway. Methods: A total of 24 healthy male Sprague-Dawley (SD) rats were divided into normal and atherosclerosis groups. The atherosclerosis rats were assigned into blank, negative control (NC), miR-22 mimic, miR-22 inhibitor and miR-22 inhibitor + siNLRP3 groups. A luciferase reporter gene assay was used to detect the relationship between miR-22 and NLRP3. MiR-22 expression as well as NLRP3 and caspase-1 mRNA and protein expression were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The activity and apoptosis of coronary arterial endothelial cells (CAECs) were determined by MTT and Hoechst 33258. CAEC lumen formation was detected by a lumen formation assay. An enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1β, IL-6, IL-10 and IL-18 levels. Results: The results indicated that the atherosclerosis group significantly decreased miR-22 expression but increased NLRP3 and caspase-1 mRNA and protein expression. The cell survival rate was significantly increased in the miR-22 mimic group and significantly reduced in the miR-22 inhibitor group. The miR-22 mimic group displayed a lower apoptosis rate and more cells with obvious lumen walls and numerous tubular structures, while cells in the miR-22 inhibitor group were unable to form lumen walls and had a scattered distribution compared to the blank group. The ELISA showed that IL-1β, IL-6 and IL-18 levels were markedly decreased, while IL-10 was clearly increased in the miR-22 mimic group. In contrast, in the miR-22 inhibitor group, IL-1β, IL-6 and IL-18 levels were significantly increased, and IL-10 levels were decreased. Conclusion: Our findings indicated that miR-22 could lower the levels of pro-inflammatory cytokines by inhibiting the NLRP3 inflammasome pathway, which suppresses CAEC apoptosis and protects CAECs in rats with CHD.

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Section: Discussionsupporting

confidence: 71%

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Huang

Wei

Lin

et al. 2017

Cell Physiol Biochem

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“…67 Furthermore, in an adjuvant-induced arthritis model in rats, upregulation of NLRP3 inflammasome components was observed in fibroblast-like cells isolated from the synovium. 68,69 These results are in line with results obtained in mice lacking the A20/Tnfaip3 gene, which predispose them to an RA-like disease. In this animal model of RA, the expression of NLRP3 inflammasome components is enhanced in macrophages and NLRP3 deficiency suppressed arthritis development and cartilage destruction.…”

Section: Infl Amma Some In Rheumatoid Arthritissupporting

confidence: 85%

“…The severity of arthritis clinical score showed a positive correlation with NLRP3 levels in synovial tissue, and clinical features of arthritic disease could be inhibited by suppression of the NLRP3 inflammasome in macrophages . Furthermore, in an adjuvant‐induced arthritis model in rats, upregulation of NLRP3 inflammasome components was observed in fibroblast‐like cells isolated from the synovium . These results are in line with results obtained in mice lacking the A20/Tnfaip3 gene, which predispose them to an RA‐like disease.…”

Section: Inflammasome In Rheumatoid Arthritissupporting

confidence: 85%

Inflammasomes contributing to inflammation in arthritis

Spel

Martinon

2020

Immunological Reviews

125

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Inflammasomes are intracellular multiprotein signaling platforms that initiate inflammatory responses in response to pathogens and cellular damage. Active inflammasomes induce the enzymatic activity of caspase‐1, resulting in the induction of inflammatory cell death, pyroptosis, and the maturation and secretion of inflammatory cytokines IL‐1β and IL‐18. Inflammasomes are activated in many inflammatory diseases, including autoinflammatory disorders and arthritis, and inflammasome‐specific therapies are under development for the treatment of inflammatory conditions. In this review, we outline the different inflammasome platforms and recent findings contributing to our knowledge about inflammasome biology in health and disease. In particular, we discuss the role of the inflammasome in the pathogenesis of arthritic diseases, including rheumatoid arthritis, gout, ankylosing spondylitis, and juvenile idiopathic arthritis, and the potential of newly developed therapies that specifically target the inflammasome or its products for the treatment of inflammatory diseases.

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“…These data indicated that endothelial cells and myeloid-derived cells might be the major source of NLRP3 inflammasome in RA. In contrast, fibroblast-like synoviocytes isolated from the adjuvant-induced arthritis model were reported to express higher levels of NLRP3 inflammasome compared to normal mice [31]. In this study, we found that active caspase-1, a downstream molecule of NLRP3 activation, was increased significantly in synovia of RA and was expressed almost exclusively in CD14positive cells but not in CD3-positive cells and cadherin-11-positive FLS, indicating that monocytes and macrophages were the major cells with activated NLRP3 inflammasome in the synovia of RA.…”

Section: Discussionmentioning

confidence: 91%

NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid arthritis

Guo

Wang

et al. 2018

Clinical and Experimental Immunology

217

180

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Summary Nucleotide‐binding, oligomerization domain (NOD)‐like receptor family, pyrin domain containing 3 (NLRP3) gene polymorphism was reported to be associated with susceptibility, disease activity or anti‐tumour necrosis factor (TNF) treatment response in rheumatoid arthritis (RA). However, the roles of NLRP3 inflammasome in the development of RA have not yet been elucidated fully. The present study aimed to study the role of NLRP3 inflammasome in RA. NLRP3 inflammasome activation in synovial tissues from RA and osteoarthritis (OA) patients were assessed by Western blot. Active caspase‐1 in synovia was stained by a FAM‐FLICA caspase‐1 probe. Mice with collagen‐induced arthritis (CIA) were treated with MCC950, a selective NLRP3 inhibitor, or vehicle for 2 weeks. The clinical score of arthritis, synovial inflammation and cartilage erosion were assessed. Proinflammatory cytokines were measured by enzyme‐linked immunosorbent assay (ELISA). The results showed that NLRP3 inflammasome was highly activated in both synovia from RA patients and CIA mice. Activation of NLRP3 inflammasome occurred mainly in the infiltrating monocyte/macrophages in synovia, but not in fibroblast‐like synoviocytes. Treatment with MCC950 resulted in significantly less severe joints inflammation and bone destruction. NLRP3 inflammasome activation in the synovia was inhibited significantly by MCC950 with reduced production of interleukin (IL)‐1β. The inhibition of NLRP3 inflammasome activation by MCC950 was confirmed further in a human monocytic cell line, THP‐1. In conclusion, NLRP3 inflammasome is involved in the pathogenesis of RA. Targeting NLRP3 inflammasome with a small molecule inhibitor might be a novel therapeutic strategy for RA.

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MicroRNA-20a negatively regulates expression of NLRP3-inflammasome by targeting TXNIP in adjuvant-induced arthritis fibroblast-like synoviocytes

Cited by 87 publications

References 35 publications

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Inflammasomes contributing to inflammation in arthritis

NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid arthritis

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