IL-21 Is Positively Associated with Intervertebral Disc Degeneration by Interaction with TNF-α Through the JAK-STAT Signaling Pathway
IL-21 Is Positively Associated with Intervertebral Disc Degeneration by Interaction with TNF-α Through the JAK-STAT Signaling Pathway
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IL-21 通过 JAK-STAT 信号通路与 TNF-α 相互作用，与椎间盘退变呈正相关
DOI：
10.1007/s10753-017-0508-6
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发表时间：
2017-04-01
期刊：
影响因子：
5.1
通讯作者：
Cheng, Lei
中科院分区：
文献类型：
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作者：
Chen, Bin;Liu, Yi;Cheng, Lei
本研究旨在探讨IL-21在椎间盘退变中的作用。采用酶联免疫吸附试验（ELISA）检测腰椎间盘突出症（LDH）患者血清IL-21水平。采用免疫组化和Western blot方法检测退变椎间盘组织中IL-21、具有血小板反应蛋白基序的去整合素和金属蛋白酶（ADAMTS-7）和肿瘤坏死因子α（TNF-α）的表达。此外，髓核（NP）细胞用0、10、100和1000 ng/mL的IL-21细胞因子处理，有和没有AG 490。RT-PCR检测TNF-α、ADAMTS-7和基质金属蛋白酶-13（MMP-13）mRNA表达。Western blot检测细胞内信号转导和转录激活因子STAT-1、STAT-3和STAT-5 b的表达。退变组IL-21水平较高，与视觉模拟评分（VAS）呈正相关。IL-21、ADAMTS-7和TNF-α可在人和大鼠退化的NP组织中的退化的NP组织中检测到。IL-21刺激后ADAMTS-7、TNF-α和MMP-13的mRNA表达增强。与对照组相比，IL-21处理后STAT-1、STAT-3和STAT-5 b的表达也增强，其中STAT-3的增强最显著;此外，用AG 490处理后表达显著降低。与单独用IL-21处理相比，AG 490处理后TNF-α mRNA表达显著降低。IL-21参与了IVD退变的病理过程，IL-21通过STAT信号通路刺激TNF-α而加重IVD退变。
This study was conducted in order to investigate the function of IL-21 in intervertebral disc degeneration. The serum concentration of IL-21 in patients with lumbar disc herniation (LDH) was examined by ELISA. Immunohistochemistry and western blot analysis were performed to detect the expression of IL-21, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-7), and tumor necrosis factor alpha (TNF-α) in degenerated intervertebral disc (IVD) tissues of human and rat. Moreover, nucleus pulposus (NP) cells were treated with 0, 10, 100, and 1000 ng/mL of IL-21 cytokine with and without AG490. TNF-α, ADAMTS-7, and matrix metalloproteinases-13 (MMP-13) mRNA expression was determined by RT-PCR. The expression of signal transducers and activators of transcription, STAT-1, STAT-3, and STAT-5b, was detected by western blot. IL-21 concentration level is higher in the degenerated group and positively correlates with the visual analog score (VAS). IL-21, ADAMTS-7, and TNF-α can be detected in the degenerative NP tissues in both human and rat degenerated NP tissues. The mRNA expression of ADAMTS-7, TNF-α, and MMP-13 was enhanced after stimulation with IL-21. Compared to control, STAT-1, STAT-3, and STAT-5b expression was also enhanced after IL-21 treatment, with STAT-3 being the most significantly enhanced; furthermore, expression was significantly reduced after treatment with AG490. The mRNA expression of TNF-α was markedly reduced after treatment with AG490 compared to treatment with IL-21 only. IL-21 is involved in the pathological development of IVD degeneration and IL-21 could aggravate IVD degeneration by stimulating TNF-α through the STAT signaling pathway.