title: Anti-Inflammatory Effects of TRAF-Interacting Protein in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.
abstract: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammatory cell infiltration, synovial inflammation, and cartilage destruction. Proliferative fibroblast-like synoviocytes (FLS) play crucial roles in both propagation of inflammation and joint damage because of their production of great amount of proinflammatory cytokines and proteolytic enzymes. In this study, we investigate the role of TRAF-interacting protein (TRIP) in regulating inflammatory process in RA-FLS. TRIP expression was attenuated in RA-FLS compared with osteoarthritis- (OA-) FLS. Overexpression of TRIP significantly inhibited the activation of NF-κB signaling and decreased the production of proinflammatory cytokines and matrix metalloproteinases (MMPs) in TNFα-stimulated RA-FLS. Furthermore, TRIP was found to interact with transforming growth factorβ-activated kinase 1 (TAK1) and promoting K48-linked polyubiquitination of TAK1 in RA-FLS. Our results demonstrate that TRIP has anti-inflammatory effects on RA-FLS and suggest TRIP as a potential therapeutic target for human RA.
authors.affiliation: Department of Orthopedic Trauma, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 06700, China.
authors.forename: Qing-Zhu
authors.identifier: 0000-0001-7797-7889
authors.initials: QZ
authors.lastname: Kong
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 06700, China.
authors.forename: Li-Tao
authors.identifier: 0000-0002-5974-8510
authors.initials: LT
authors.lastname: Guo
authors.affiliation: Department of Spinal Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 06700, China.
authors.forename: Jia-Ning
authors.identifier: 0000-0002-4767-0728
authors.initials: JN
authors.lastname: Yang
authors.affiliation: Department of Emergency, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 06700, China.
authors.forename: Yan-Fei
authors.identifier: 0000-0003-4951-040X
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Trauma, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 06700, China.
authors.forename: Jing-Xin
authors.identifier: 0000-0002-0897-1683
authors.initials: JX
authors.lastname: Zhao
authors.affiliation: Department of Gynaecology and Obstetrics, Maternal and Child Health Care Hospital of Longhua County, Chengde, Hebei 068150, China.
authors.forename: Su-Hong
authors.identifier: 0000-0001-5245-9591
authors.initials: SH
authors.lastname: Kong
authors.affiliation: Department of Emergency, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 06700, China.
authors.forename: Meng
authors.identifier: 0000-0001-9225-0864
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Trauma, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 06700, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Orthopedic Trauma, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 06700, China.
authors.forename: Yu
authors.identifier: 0000-0002-1298-8242
authors.initials: Y
authors.lastname: Jin
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016086:Lentivirus; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism*; D015398:Signal Transduction; D013582:Synovial Fluid / Q000378:metabolism; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D020930:MAP Kinase Kinase Kinases; D020781:Matrix Metalloproteinase 1; D053509:Matrix Metalloproteinase 13; D016328:NF-kappa B; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D044767:Ubiquitin-Protein Ligases; D000099151:MAP Kinase Kinase Kinase 7; C508585:IL1B protein, human; C508600:IL6 protein, human; C000607340:TRAIP protein, human; C507079:MMP13 protein, human; C522360:MMP1 protein, human