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

AI Article Synopsis

  • - Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting about 1% of the population, characterized by inflammation from abnormal synoviocyte behavior and increased cytokine production.
  • - The study focused on ubiquitin-specific protease 5 (USP5), finding that its expression is higher in RA fibroblast-like synoviocytes (FLS) compared to osteoarthritis FLS, with IL-1 further increasing USP5 levels.
  • - Overexpressing USP5 worsened inflammation and activated key signaling pathways, while silencing USP5 reduced cytokine release; it also stabilizes TRAF6 by removing its ubiquitination, highlighting USP5 as a potential therapeutic target for RA.

Article Abstract

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-1 stimulation increased USP5 expression in a time-dependent manner. Furthermore, we found that USP5 overexpression significantly aggravated proinflammatory cytokine production and related nuclear factor B (NF-B) signaling activation. Consistently, silencing of USP5 decreased the release of cytokines and inhibited the activation of NF-B. 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085372PMC
http://dx.doi.org/10.1155/2020/8295149DOI Listing

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