<scp>NLRP</scp>6 facilitates the interaction between <scp>TAB</scp>2/3 and <scp>TRIM</scp>38 in rheumatoid arthritis fibroblast‐like synoviocytes

Yang, Lin; Luo, Zhitian

doi:10.1002/1873-3468.12622

Cited by 30 publications

(21 citation statements)

References 24 publications

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“…The cells were lysed using RIPA buffer (Thermo Fisher Scientific, Inc.), and total protein in the supernatants was quantified using a BcA protein assay kit (Thermo Fisher Scientific, Inc.). IP and western blot analysis were performed as described previously (27). Equal amounts of protein (50 µg protein per lane) were loaded on 10% SdS-PAGE for separating them and then transferred to polyvinylidene fluoride membranes (EMD Millipore, Billerica, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Effect of deubiquitinase USP8 on hypoxia/reoxygenation‑induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells

et al. 2018

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Intermittent hypoxia/reoxygenation (IHR), characterized by repeated episodes of hypoxia interspersed with periods of reoxygenation, has been found to induce pro‑inflammatory cytokine production and is increasingly recognized as a major pathophysiological factor in various disease processes with distinct cell and molecular responses. The present study is the first, to the best of our knowledge, to investigate the effects of ubiquitin‑specific peptidase 8 (USP8) on IHR‑induced inflammation in renal tubular epithelial cells and examine the underlying mechanism. Following transfection of plasmids, HK‑2 and TCMK‑1 cells were incubated for eight cycles of IHR treatment including 3 h of hypoxic incubation followed by 3 h of normoxic culture. It was demonstrated that the expression of USP8 was decreased in IHR conditions but not in normoxic or continuous hypoxic conditions. In addition, IHR‑induced inflammation was suppressed in USP8‑overexpressinh renal tubular epithelial cells, and the silencing of USP8 markedly aggravated inflammation. Furthermore, it was found that the overexpression of USP8 inhibited the IHR‑induced activation of nuclear factor‑κB and it was demonstrated that USP8 interacted with transforming growth factor‑β‑activated kinase‑1 (TAK1) and deubiquitinated the K63‑linked ubiquitination of TAK1. Taken together, the results demonstrated the role of USP8 in IHR‑induced inflammation and suggested USP8 as a potential and specific therapeutic target for IHR‑related diseases.

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Section: Methodsmentioning

confidence: 99%

Effect of deubiquitinase USP8 on hypoxia/reoxygenation‑induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells

et al. 2018

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“…Treated RA-FLS. Recently, many studies showed that NF-κB signaling is crucial for the RA process, especially in the proinflammatory cytokine production in FLS [4,9,16]. Therefore, we detected the effect of USP5 on IL-1β-induced NF-κB activation.…”

Section: Usp5 Promoted Nf-κb Signaling Activation In Il-1β-mentioning

confidence: 84%

“…Dual-Luciferase Reporter Gene Assays. The experiments were performed as described in [16]. Luciferase activity of the NF-κB promoter was evaluated by the Dual-Luciferase Reporter Assay System (Promega, Madison, USA) and detected by a spectraMax M5 reader (Molecular Devices, California, USA).…”

Section: Western Blot Analysis Immunoprecipitation Andmentioning

confidence: 99%

Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Luo

Liu

et al. 2020

Mediators of Inflammation

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Rheumatoid arthritis (RA) is a worldwide chronic autoimmune inflammatory disease which is affecting approximately 1% of the total population. It is characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS) and increased production of proinflammatory cytokines. In the current study, we were aiming to investigate the role of ubiquitin-specific protease 5 (USP5) in the inflammatory process in RA-FLS. Expression of USP5 was found upregulated in RA-FLS compared with that in osteoarthritis- (OA-) FLS, and IL-1β stimulation increased USP5 expression in a time-dependent manner. Furthermore, we found that USP5 overexpression significantly aggravated proinflammatory cytokine production and related nuclear factor κB (NF-κB) signaling activation. Consistently, silencing of USP5 decreased the release of cytokines and inhibited the activation of NF-κB. In addition, USP5 was found to interact with tumor necrosis factor receptor-associated factor 6 (TRAF6) and remove its K48-linked polyubiquitination chains therefore stabilizing TRAF6. Our data showed that a USP5-positive cell regulates inflammatory processes in RA-FLS and suggested USP5 as a potential target for RA treatment.

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“…In this study, NLRP6 was found to be downregulated in synovial tissues and fibroblast-like synoviocytes (FLS) at both the transcription and translational levels in rheumatoid arthritis patients compared to osteoarthritis patients. 69 Silencing of NLRP6 in FLS from rheumatoid arthritis patients enhanced proinflammatory cytokine production via increased activity of NF-κB in response to TNF-α. Furthermore, the authors reported that NLRP6 acted as a docking site to facilitate the interaction between transforming growth factor-βactivated kinase-1 binding protein 2/3 and tripartite motif 38 to promote lysosome-dependent degradation.…”

Section: Nlrp6 In Human Diseasesmentioning

confidence: 99%

“…Furthermore, the authors reported that NLRP6 acted as a docking site to facilitate the interaction between transforming growth factor-βactivated kinase-1 binding protein 2/3 and tripartite motif 38 to promote lysosome-dependent degradation. 69 It is interesting that NLRP6 was found to regulate lysosome-mediated degradation, although future studies are needed to investigate if these findings have clinical relevance in other diseases.…”

Section: Nlrp6 In Human Diseasesmentioning

confidence: 99%

The NLRP6 inflammasome in health and disease

et al. 2020

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NACHT, LRR (leucine-rich repeat), and PYD (pyrin domain) domain-containing 6 (Nlrp6) is a member of the NLR (nucleotideoligomerization domain-like receptor) family that patrols the cytosolic compartment of cells to detect pathogen-and damageassociated molecular patterns. Because Nlrp6 is a recently discovered inflammasome, details of its signaling mechanism, structural assembly, and roles in host defense have yet to be determined. To date, Nlrp6 has been proposed to perform a multitude of functions ranging from control of microbiota, maintenance of epithelial integrity, and regulation of metabolic diseases to modulation of host defense during microbial infections, cancer protection, and regulation of neuroinflammation. While recent studies have questioned some of the proposed functions of Nlrp6, Nlrp6 has been shown to form an inflammasome complex and cleaves interleukin-1β (IL-1β) and IL-18 during microbial infection, indicating that it is a bonafide inflammasome. In this review, we summarize the recent advancements in knowledge of the signaling mechanisms and structure of the Nlrp6 inflammasome and discuss the relevance of NLRP6 to human disease.

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NLRP6 facilitates the interaction between TAB2/3 and TRIM38 in rheumatoid arthritis fibroblast‐like synoviocytes

Cited by 30 publications

References 24 publications

Effect of deubiquitinase USP8 on hypoxia/reoxygenation‑induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells

Effect of deubiquitinase USP8 on hypoxia/reoxygenation‑induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells

Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

The NLRP6 inflammasome in health and disease

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