Functional proteomics revealed IL-1β amplifies TNF downstream protein signals in human synoviocytes in a TNF-independent manner

被引:41
作者
Shen, Shan [1 ,2 ]
Guo, Jiahui [2 ]
Luo, Yanzhang [2 ]
Zhang, Wanling [2 ]
Cui, Yizhi [2 ]
Wang, Qing [2 ]
Zhang, Zhiguang [1 ]
Wang, Tong [2 ]
机构
[1] Sun Yat Sen Univ, Guangdong Prov Key Lab Stomatol, Dept Oral & Maxillofacial Surg, Guanghua Sch Stomatol,Hosp Stomatol, Guangzhou 510055, Guangdong, Peoples R China
[2] Jinan Univ, Guangdong Higher Educ Inst, Inst Life & Hlth Engn,Affiliated Hosp 1, Key Lab Funct Prot Res,Coll Life Sci & Technol, Guangzhou 510632, Guangdong, Peoples R China
关键词
Synoviocytes; IL-1; beta; Proteomics; TNF-independent; p62; EARLY RHEUMATOID-ARTHRITIS; NF-KAPPA-B; DISEASE-ACTIVITY; OSTEOARTHRITIS; THERAPY; PATHOGENESIS; PATHWAYS; EFFICACY; ALPHA; MRI;
D O I
10.1016/j.bbrc.2014.06.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
IL-1 beta is readily detectable in numerous joint inflammations. It can change the transcriptomic signature of fibroblast-like synoviocytes (FLS) of arthritis toward promoting migration and invasion that are relevant to arthritis progression. We hypothesize that IL-1 beta partially contributes to the onset of osteoarthritis (OA). We compared the tissue samples from OA and fracture subjects and found that IL-1 beta expression was significantly higher in the OA synovium, while TNF-alpha expression showed no significance. We demonstrated that IL-1 beta significantly increases the IL-6 and IL-8 secretions of human normal FLS; however, IL-1 beta does not induce TNF secretion. With metabolic labeling based proteomics and pathway analysis, we found that IL-1 beta significantly increases the TNF downstream protein expression in FLS even with complete absence of TNF and/or blocking of the NF-kappa B pathway. Among these proteins, we verified that p62 can differentiate the OA from fracture synovitis. In conclusion, we demonstrated that IL-1 beta can amplify the TNF downstream protein signals in human synoviocytes in a TNF-independent manner; in addition, p62 is a potential FLS biomarker for synovitis. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:538 / 544
页数:7
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