Deep Coverage Tissue and Cellular Proteomics Revealed IL-1β Can Independently Induce the Secretion of TNF-Associated Proteins from Human Synoviocytes
| Autor: | Tong Wang, Ziqi Yan, Yanzhang Luo, Wanling Zhang, Shengquan Tang, Shan Shen, Qing-Yu He, Suyuan Deng, Yizhi Cui, Xing Chen, Jiahui Guo |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteomics Immunology Interleukin-1beta Endocytosis 03 medical and health sciences symbols.namesake 0302 clinical medicine Osteoarthritis Immunology and Allergy Humans Secretion Cell Proliferation 030203 arthritis & rheumatology Synovitis Chemistry Endoplasmic reticulum Synovial Membrane Computational Biology Golgi apparatus Fibroblasts Phosphoproteins Synoviocytes Complement system Cell biology 030104 developmental biology Secretory protein Tumor Necrosis Factors symbols Tumor necrosis factor alpha Carrier Proteins Biomarkers Protein Binding Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 200(2) |
| ISSN: | 1550-6606 |
| Popis: | Synovitis is a key contributor to the inflammatory environment in osteoarthritis (OA) joints. Currently, the biological therapy of OA is not satisfactory in multiple single-target trials on anti-TNF agents, or IL-1 antagonists. Systems biological understanding of the phosphorylation state in OA synovium is warranted to direct further therapeutic strategies. Therefore, in this study, we compared the human synovial phosphoproteome of the OA with the acute joint fracture subjects. We found that OA synovium had significantly more phosphoproteins, and 82 phosphoproteins could only be specifically found in all the OA samples. Differentially expressed proteins of the OA synovium were focusing on endoplasmic reticulum–/Golgi-associated secretion and negative regulation of cell proliferation, which was verified through an IL-1β–treated human synoviocyte (HS) in vitro model. With data-independent acquisition–based mass spectrometry, we found that IL-1β could induce HS to secrete proteins that were significantly associated with the endosomal/vacuolar pathway, endoplasmic reticulum/Golgi secretion, complement activation, and collagen degradation. Especially, we found that while specifically suppressing HS endocytosis, IL-1β could activate the secretion of 25 TNF-associated proteins, and the change of SERPINE2 and COL3A1 secretion was verified by immunoblotting. In conclusion, our results suggest that OA synovium has a polarized phosphoproteome to inhibit proliferation and maintain active secretion of HS, whereas IL-1β alone can transform HS to produce a synovitis-associated secretome, containing numerous TNF-associated secretory proteins in a TNF-independent mode. |
| Databáze: | OpenAIRE |
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