Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes
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 stud...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/8295149 |
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| author | Xiao-Bo Luo Jian-Cheng Xi Zhen Liu Yu Long Li-tao Li Zhan-Peng Luo Dao-Hong Liu |
| author_facet | Xiao-Bo Luo Jian-Cheng Xi Zhen Liu Yu Long Li-tao Li Zhan-Peng Luo Dao-Hong Liu |
| author_sort | Xiao-Bo Luo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f2c849775e6d49caa2fdfd8df6a69e37 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-f2c849775e6d49caa2fdfd8df6a69e372025-08-20T03:25:42ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/82951498295149Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like SynoviocytesXiao-Bo Luo0Jian-Cheng Xi1Zhen Liu2Yu Long3Li-tao Li4Zhan-Peng Luo5Dao-Hong Liu6Department of Orthopedic, Eighth Medical Center of PLA General Hospital, Beijing 100091, ChinaDepartment of Orthopedic, Eighth Medical Center of PLA General Hospital, Beijing 100091, ChinaDepartment of Orthopedic, Eighth Medical Center of PLA General Hospital, Beijing 100091, ChinaDepartment of Orthopedic, Eighth Medical Center of PLA General Hospital, Beijing 100091, ChinaDepartment of Orthopedic, Eighth Medical Center of PLA General Hospital, Beijing 100091, ChinaDepartment of Orthopedic, Eighth Medical Center of PLA General Hospital, Beijing 100091, ChinaDepartment of Orthopedic, Eighth Medical Center of PLA General Hospital, Beijing 100091, ChinaRheumatoid 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.http://dx.doi.org/10.1155/2020/8295149 |
| spellingShingle | Xiao-Bo Luo Jian-Cheng Xi Zhen Liu Yu Long Li-tao Li Zhan-Peng Luo Dao-Hong Liu Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes Mediators of Inflammation |
| title | Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes |
| title_full | Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes |
| title_fullStr | Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes |
| title_full_unstemmed | Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes |
| title_short | Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes |
| title_sort | proinflammatory effects of ubiquitin specific protease 5 usp5 in rheumatoid arthritis fibroblast like synoviocytes |
| url | http://dx.doi.org/10.1155/2020/8295149 |
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