IL-10 通过抑制 p38 MAPK 信号通路延缓椎间盘退变。
IL-10 delays the degeneration of intervertebral discs by suppressing the p38 MAPK signaling pathway.
机构信息
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China.
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China.
出版信息
Free Radic Biol Med. 2020 Feb 1;147:262-270. doi: 10.1016/j.freeradbiomed.2019.12.040. Epub 2019 Dec 25.
OBJECTIVES
The degeneration of intervertebral discs (IVD) is a risk factor for chronic low back pain. Anti-inflammation therapy could alleviate IVD degeneration. IL-10 is an important anti-inflammatory cytokine. However, the effect of IL-10 on IVD has not been fully revealed. The current study is to reveal the effect of IL-10 on IVD and its underlying mechanism.
METHODS
IL-1β was used to induce the degeneration of nucleus pulposus cells (NPCs). mRNA expression level was determined by qPCR. Protein expression level was determined by western blotting. Methylene blue was used to determined the expression of aggrecan. Immunocytochemical staining was used to determined the expression of collagen II. A rat caudal IVD degeneration model was established and used to evaluate the effect of IL-10 on IVD in vivo.
RESULTS
IL10 could alleviated NPC degeneration in both morphology and extracellular matrix. IL-10 could increase the mRNA expression of Collagen II, Sox-9, but decrease the mRNA expression of IL-1β, TNFα and Collagen X. IL-10 could also increase the protein level of Collagen II and aggrecan, but decrease that of Collagen X. Western blotting futher revealed the mechanism of the positive effect of IL-10 on IVD. IL-10 reduces phosphorylation level of p38 MAPK effectively. Rat caudal IVD degeneration model futher confirmed the positive effect of IL-10 on IVD degeneration and its mechanism in vivo.
CONCLUSION
The current study demonstrates that exogenous IL-10 treatment can induce an anti-inflammatory response and inhibit p38 MAPK activation to delay IVD degeneration.
目的
椎间盘（IVD）退变是慢性下腰痛的危险因素。抗炎治疗可以缓解 IVD 退变。IL-10 是一种重要的抗炎细胞因子。然而，IL-10 对 IVD 的作用尚未完全揭示。本研究旨在揭示 IL-10 对 IVD 的作用及其潜在机制。
方法
用 IL-1β诱导髓核细胞（NPC）退变。通过 qPCR 测定 mRNA 表达水平。通过 Western blot 测定蛋白表达水平。亚甲蓝用于测定聚集蛋白聚糖的表达。免疫细胞化学染色用于测定胶原 II 的表达。建立大鼠尾椎 IVD 退变模型，用于体内评价 IL-10 对 IVD 的作用。
结果
IL10 可减轻 NPC 在形态和细胞外基质方面的退变。IL-10 可增加 Collagen II、Sox-9 的 mRNA 表达，降低 IL-1β、TNFα 和 Collagen X 的 mRNA 表达。IL-10 还可增加 Collagen II 和聚集蛋白聚糖的蛋白水平，降低 Collagen X 的蛋白水平。Western blot 进一步揭示了 IL-10 对 IVD 产生正向作用的机制。IL-10 可有效降低 p38 MAPK 的磷酸化水平。大鼠尾椎 IVD 退变模型进一步证实了 IL-10 对 IVD 退变及其在体内的作用机制。
结论
本研究表明，外源性 IL-10 治疗可诱导抗炎反应并抑制 p38 MAPK 激活，从而延缓 IVD 退变。
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