基质金属蛋白酶
体内
体外
椎间盘
免疫印迹
化学
p38丝裂原活化蛋白激酶
退行性椎间盘病
药理学
污渍
炎症
细胞生物学
免疫学
分子生物学
医学
信号转导
病理
生物
生物化学
解剖
MAPK/ERK通路
生物技术
替代医学
基因
作者
Olga Krupková,Miho Sekiguchi,Juergen Klasen,Oliver Hausmann,Satoshi Konno,Stephen J. Ferguson,Karin Wuertz‐Kozak
摘要
Intervertebral disc (IVD) disease, which is characterised by age-related changes in the adult disc, is the most common cause of disc failure and low back pain. The purpose of this study was to analyse the potential of the biologically active polyphenol epigallocatechin 3-gallate (EGCG) for the treatment of painful IVD disease by identifying and explaining its anti-inflammatory and anti-catabolic activity. Human IVD cells were isolated from patients undergoing surgery due to degenerative disc disease (n = 34) and cultured in 2D or 3D. An inflammatory response was activated by IL-1β, EGCG was added, and the expression/activity of inflammatory mediators and pathways was measured by qRT-PCR, western blotting, ELISA, immunofluorescence and transcription factor assay. The small molecule inhibitor SB203580 was used to investigate the involvement of the p38 pathway in the observed effects. The analgesic properties of EGCG were analysed by the von Frey filament test in Sprague-Dawley rats (n = 60). EGCG significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-κB.
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