功能蛋白质组学揭示白细胞介素-1β（IL-1β）以 TNF 非依赖的方式放大人滑膜细胞中 TNF 的下游蛋白信号。
Functional proteomics revealed IL-1β amplifies TNF downstream protein signals in human synoviocytes in a TNF-independent manner.
机构信息
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.
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.
出版信息
Biochem Biophys Res Commun. 2014 Jul 18;450(1):538-44. doi: 10.1016/j.bbrc.2014.06.008. Epub 2014 Jun 10.
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.
IL-1β 在许多关节炎症中都能被轻易检测到。它可以改变关节炎成纤维样滑膜细胞（FLS）的转录组特征，促进与关节炎进展相关的迁移和侵袭。我们假设 IL-1β 部分导致了骨关节炎（OA）的发生。我们比较了 OA 和骨折患者的组织样本，发现 OA 滑膜中的 IL-1β 表达明显更高，而 TNF-α 的表达则没有显著差异。我们证明，IL-1β 显著增加了人正常 FLS 的 IL-6 和 IL-8 的分泌；然而，IL-1β 并不诱导 TNF 的分泌。通过基于代谢标记的蛋白质组学和通路分析，我们发现，即使在完全缺乏 TNF 和/或阻断 NF-κB 通路的情况下，IL-1β 也能显著增加 FLS 中 TNF 下游蛋白的表达。在这些蛋白质中，我们验证了 p62 可以区分 OA 和骨折性滑膜炎。总之，我们证明了 IL-1β 可以以 TNF 非依赖性的方式放大人滑膜细胞中 TNF 下游蛋白的信号；此外，p62 是滑膜细胞的一个潜在的 FLS 生物标志物。
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