IL-1β/HMGB1 signalling promotes the inflammatory cytokines release via TLR signalling in human intervertebral disc cells.
IL-1β/HMGB1 signalling promotes the inflammatory cytokines release via TLR signalling in human intervertebral disc cells.
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DOI：
10.1042/bsr20160118
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发表时间：
2016-10
影响因子：
4
通讯作者：
Jiang D
中科院分区：
文献类型：
--
作者：
Fang F;Jiang D
炎症和细胞因子通过调节临床症状和体征的发展而被认为与椎间盘退行性变(IDD)相关。然而，监管机制仍不清楚。本研究旨在研究白细胞介素1(IL-β)和高迁移率族蛋白1(HMGB1)在人血管内皮细胞炎症反应中的调节作用，并探讨介导这种调节作用的信号通路。首先，用ELISA法检测IVD细胞对炎性细胞因子的促进作用。免疫印迹和实时定量聚合酶链式反应分析IL-1HMGB1诱导的IVD细胞中Toll样受体(TLRs)、晚期糖基化终产物受体(RAGE)和核因子-κB信号标志物的表达。结果表明，IL-1β或HMGB1均能促进人IVD细胞释放前列腺素E_2、肿瘤坏死因子-α、IL-6和IL-8等炎性细胞因子。IL-1β和HMGB1对基质金属蛋白酶的表达也有上调作用。我们还发现这种相加促进TLR2、TLR4和RAGE的表达，以及在椎间盘细胞中的NF-κB信号转导。综上所述，我们的研究表明，IL-1、β和HMGB1共同促进了炎性细胞因子的释放和MMPs的表达。IL-1、κ和HMGB1对TLRs、RAGE和NF-βB信号通路也有相加的促进作用。提示IL-1、β和HMGB1对炎性细胞因子和MMPs的相加促进作用可能加重了IDD的进展。
Inflammation and cytokines have been recognized to correlate with intervertebral disc (IVD) degeneration (IDD), via mediating the development of clinical signs and symptoms. However, the regulation mechanism remains unclear. We aimed at investigating the regulatory role of interleukin (IL)β and high mobility group box 1 (HMGB1) in the inflammatory response in human IVD cells, and then explored the signalling pathways mediating such regulatory effect. Firstly, the promotion to inflammatory cytokines in IVD cells was examined with ELISA method. And then western blot and real time quantitative PCR were performed to analyse the expression of toll-like receptors (TLRs), receptors for advanced glycation endproducts (RAGE) and NF-κB signalling markers in the IL-1β- or (and) HMGB1-treated IVD cells. Results demonstrated that either IL-1β or HMGB1 promoted the release of the inflammatory cytokines such as prostaglandin E2 (PGE2), TNF-α, IL-6 and IL-8 in human IVD cells. And the expression of matrix metalloproteinases (MMPs) such as MMP-1, -3 and -9 was also additively up-regulated by IL-1β and HMGB1. We also found such additive promotion to the expression of TLR-2, TLR-4 and RAGE, and the NF-κB signalling in intervertebral disc cells. In summary, our study demonstrated that IL-1β and HMGB1 additively promotes the release of inflammatory cytokines and the expression of MMPs in human IVD cells. The TLRs and RAGE and the NF-κB signalling were also additively promoted by IL-1β and HMGB1. Our study implied that the additive promotion by IL-1β and HMGB1 to inflammatory cytokines and MMPs might aggravate the progression of IDD.