IL-10 delays the degeneration of intervertebral discs by suppressing the p38 MAPK signaling pathway
IL-10 delays the degeneration of intervertebral discs by suppressing the p38 MAPK signaling pathway
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IL-10通过抑制p38 MAPK信号通路延缓椎间盘退变
DOI：
10.1016/j.freeradbiomed.2019.12.040
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发表时间：
2020-02-01
影响因子：
7.4
通讯作者：
Zou, Jun
中科院分区：
文献类型：
--
作者：
Ge, Jun;Yan, Qi;Zou, Jun
目的：椎间盘退变（IVD）是慢性腰痛的危险因素。抗炎治疗可减轻IVD变性。IL-10是一种重要的抗炎细胞因子。然而，IL-10对IVD的影响尚未完全揭示。本研究旨在探讨IL-10对椎间盘退变的影响及其机制。通过qPCR测定mRNA表达水平。蛋白质表达水平通过蛋白质印迹法测定。用亚甲蓝法检测聚集蛋白聚糖的表达。免疫细胞化学染色检测Ⅱ型胶原的表达。结果：IL-10能减轻鼻咽癌细胞形态学和细胞外基质的退变，并能促进鼻咽癌细胞的增殖和分化。IL-10可增加II型胶原、Sox-9的mRNA表达，降低IL-1 β、TNF α和X型胶原的mRNA表达。IL-10还能增加Ⅱ型胶原和聚集蛋白聚糖的蛋白水平，而降低X型胶原的蛋白水平。Western blotting进一步揭示了IL-10对IVD的积极作用机制。IL-10能有效降低p38 MAPK的磷酸化水平。结论：外源性IL-10可通过诱导抗炎反应和抑制p38 MAPK活化延缓IVD变性。
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-1 beta 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-1 beta, TNF alpha 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.