https://scholars.lib.ntu.edu.tw/handle/123456789/542166
標題: | Anti-citrullinated protein antibodies promote apoptosis of mature human Saos-2 osteoblasts via cell-surface binding to citrullinated heat shock protein 60 | 作者: | Lu M.-C. CHIA-LI YU Yu H.-C. Huang H.-B. Koo M. Lai N.-S. |
關鍵字: | Anti-citrullinated protein antibodies; Apoptosis; Dheumatoid arthritis; Heat shock protein 60; Osteoblast | 公開日期: | 2016 | 出版社: | Elsevier GmbH | 卷: | 221 | 期: | 1 | 起(迄)頁: | 76-83 | 來源出版物: | Immunobiology | 摘要: | We hypothesized that anti-citrullinated protein antibodies (ACPAs) react with osteoblast surface citrullinated proteins and affect cell function, leading to joint damage in patients with rheumatoid arthritis (RA). First, we purified ACPAs by cyclic citrullinated peptide (CCP)-conjugated affinity column chromatography. The cognate antigens of ACPAs on Saos-2 cells, a sarcoma osteogenic cell line generated from human osteoblasts, were probed by ACPAs, and the reactive bands were analyzed using proteomic analyses. We found that ACPAs bind to Saos-2 cell membrane, and several protein candidates, including HSP60, were identified. We then cloned and purified recombinant heat shock protein 60 (HSP60) and citrullinated HSP60 (citHSP60) and investigated the effect of ACPAs on Saos-2 cell. We confirmed that HSP60 obtained from Saos-2 cell membrane were citrullinated and reacted with ACPAs, which induces Saos-2 cells apoptosis via binding to surface-expressed citHSP60 through Toll-like receptor 4 signaling. ACPAs promoted interleukin (IL)-6 and IL-8 expression in Saos-2 cells. Finally, sera from patients with RA and healthy controls were examined for their titers of anti-HSP60 and anti-citHSP60 antibodies using an enzyme-linked immunosorbent assay. The radiographic change in patients with RA was evaluated using the Genant-modified Sharp scoring system. Patients with RA showed higher sera titers of anti-citHSP60, but not anti-HSP60, antibodies when compared with controls. In addition, the anti-citHSP60 level was positively associated with increased joint damage in patients with RA. In conclusion, Saos-2 cell apoptosis was mediated by ACPAs via binding to cell surface-expressed citHSP60 and the titer of anti-citHSP60 in patients with RA positively associated with joint damage. ? 2015 Elsevier GmbH. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84946492505&doi=10.1016%2fj.imbio.2015.07.019&partnerID=40&md5=4edcefdf9c1d36df0369e881012cb4c8 https://scholars.lib.ntu.edu.tw/handle/123456789/542166 |
ISSN: | 0171-2985 | DOI: | 10.1016/j.imbio.2015.07.019 | SDG/關鍵字: | chaperonin 60; citrullinated heat shock protein 60; citrullinated heat shock protein 60 antibody; cyclic citrullinated peptide antibody; heat shock protein 60 antibody; interleukin 6; interleukin 8; protein antibody; recombinant heat shock protein 60; recombinant protein; toll like receptor 4; unclassified drug; autoantibody; autoantigen; chaperonin 60; citrulline; HSPD1 protein, human; IL6 protein, human; interleukin 6; interleukin 8; mitochondrial protein; protein binding; TLR4 protein, human; toll like receptor 4; adult; antibody blood level; antibody response; antibody titer; antigen binding; apoptosis; Article; cell maturation; cell membrane; cell surface; controlled study; disease association; female; human; human cell; major clinical study; male; molecular cloning; osteoblast; pathogenesis; priority journal; protein analysis; protein binding; protein expression; proteomics; rheumatoid arthritis; Saos 2 cell line; signal transduction; aged; apoptosis; biosynthesis; case control study; cell line; drug effects; genetics; immunology; joint; metabolism; middle aged; osteoblast; pathology; protein processing; rheumatoid arthritis; Adult; Aged; Apoptosis; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Case-Control Studies; Cell Line; Chaperonin 60; Citrulline; Cloning, Molecular; Female; Humans; Interleukin-6; Interleukin-8; Joints; Male; Middle Aged; Mitochondrial Proteins; Osteoblasts; Protein Binding; Protein Processing, Post-Translational; Recombinant Proteins; Toll-Like Receptor 4 |
顯示於: | 醫學系 |
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