title: Functional proteomics revealed IL-1β amplifies TNF downstream protein signals in human synoviocytes in a TNF-independent manner.
abstract: IL-1β 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-1β partially contributes to the onset of osteoarthritis (OA). We compared the tissue samples from OA and fracture subjects and found that IL-1β expression was significantly higher in the OA synovium, while TNF-α expression showed no significance. We demonstrated that IL-1β significantly increases the IL-6 and IL-8 secretions of human normal FLS; however, IL-1β does not induce TNF secretion. With metabolic labeling based proteomics and pathway analysis, we found that IL-1β significantly increases the TNF downstream protein expression in FLS even with complete absence of TNF and/or blocking of the NF-κB pathway. Among these proteins, we verified that p62 can differentiate the OA from fracture synovitis. In conclusion, we demonstrated that IL-1β 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.
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China; Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Shen
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Guo
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
authors.forename: Yanzhang
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
authors.forename: Wanling
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China. Electronic address: drzhangzg@163.com.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China. Electronic address: tongwang@jnu.edu.cn.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology*; D013585:Synovitis / Q000378:metabolism* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D053583:Interleukin-1beta; D020543:Proteome; D014409:Tumor Necrosis Factor-alpha
keywords: IL-1β; Proteomics; Synoviocytes; TNF-independent; p62