Celastrol reduces IL-1β induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo
Celastrol reduces IL-1β induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo
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雷公藤红素可减少人髓核细胞中 IL-1 β 诱导的基质分解代谢、氧化应激和炎症，并减轻体内大鼠椎间盘退变
DOI：
10.1016/j.biopha.2017.04.093
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发表时间：
2017-07-01
影响因子：
7.5
通讯作者：
Wang, Xiang-Yang
中科院分区：
文献类型：
--
作者：
Chen, Jian;Xuan, Jun;Wang, Xiang-Yang
雷公藤红素通过抑制NF-κ B B通路对哮喘、克罗恩病、关节炎和神经退行性疾病等炎症性疾病具有治疗作用。而雷公藤红素对椎间盘退变（IDD）的影响，这也是一种促炎性疾病，仍然未知。在这项研究中，我们评估了雷公藤红素对体外IL-1 β处理的人髓核细胞以及体内穿刺诱导的大鼠IDD模型中IDD的影响。结果表明雷公藤红素可降低IL-1 β诱导的髓核细胞内分解代谢基因（MMP-3、9、13、ADAMTS-4、5）、氧化应激因子（考克斯-2、iNOS）和促炎因子（IL-6、TNF-α）的表达，并可减弱NF-κ B α和p65的磷酸化，表明雷公藤红素可抑制髓核细胞NF-κ B通路。体内研究显示雷公藤红素处理的大鼠在2周和6周时间点比溶剂处理的大鼠具有更强的T2加权信号，表明雷公藤红素可以减轻体内椎间盘退变。总之，我们的研究表明，雷公藤红素可以减少IL-1 β诱导的基质catalysts，氧化应激和炎症在人类髓核细胞和减轻大鼠椎间盘退变在体内，这表明它的潜力是IDD的治疗药物。(C)2017 Elsevier Masson SAS。All rights reserved.
Celastrol has been reported to exert therapeutic potential on pro-inflammatory diseases including asthma, Crohn's disease, arthritis and neurodegenerative disorders via inhibiting NF-kappa B pathway. While the effect of celastrol on intervertebral disc degeneration (IDD), which is also a pro-inflammatory disease, remains unknown. In this study, we evaluated the effect of celastrol on IDD in IL-1 beta treated human nucleus pulposus cells in vitro as well as in puncture induced rat IDD model in vivo. Our results showed that celastrol reduced the expression of catabolic genes (MMP-3, 9, 13, ADAMTS-4, 5), oxidative stress factors (COX-2, iNOS) and pro-inflammatory factors (IL-6, TNF-a) induced by IL-1 beta in nucleus pulposus cells, also phosphorylation of IkB alpha and p65 were attenuated by celastrol, indicating NF-kappa B pathway was inhibited by celastrol in nucleus pulposus cells. In vivo study showed that celastrol treated rats had stronger T2-weighted signal than vehicle-treated rats at 2 weeks and 6 weeks' time point, suggesting celastrol could attenuate intervertebral disc degeneration in vivo. Together, our study demonstrates that celastrol could reduce IL-1 beta induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo, which shows its potential to be a therapeutic drug for IDD. (C) 2017 Elsevier Masson SAS. All rights reserved.