Effects of IL-1 on MMP-9 Expression in Cementoblast-Derived Cell Line and MMP-Mediated Degradation of Type I Collagen
Effects of IL-1 on MMP-9 Expression in Cementoblast-Derived Cell Line and MMP-Mediated Degradation of Type I Collagen
复制标题
IL-1 对成牙骨质细胞系中 MMP-9 表达的影响以及 MMP 介导的 I 型胶原降解
DOI：
10.1007/s10753-018-00951-6
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发表时间：
2019-04-01
期刊：
影响因子：
5.1
通讯作者：
He, Hong
中科院分区：
文献类型：
--
作者：
Du, Mingyuan;Wang, Yunlong;He, Hong
基质金属蛋白酶（matrix metalloproteinases，MMPs）是一种由多种细胞因子诱导的蛋白酶，参与牙周炎等多种炎症过程。然而，白细胞介素-1（IL-1）对成牙骨质细胞（负责牙骨质生成的细胞）中MMP-9表达的影响在很大程度上仍然未知。在这项研究中，我们使用qPCR和明胶酶谱分析表明，IL-1上调MMP-9在成牙骨质细胞来源的细胞系的表达。几种信号通路，如ERK 1/2、JNK、p38和AP-1（c-Fos和ATF-2）响应于IL-1刺激而被激活。此外，AP-1报告基因分析和电泳迁移率变动分析（EMSA）进一步证实了IL-1对AP-1活性的增强作用。用ERK 1/2（U 0126）、JNK（SP 600125）和AP-1（丹参酮IIA）的特异性抑制剂预处理可减弱IL-1诱导的MMP-9表达。此外，ERK 1/2（U 0126）和JNK（SP 600125）的抑制剂减弱IL-1增强的AP-1活性。这表明IL-1至少部分通过ERK 1/2和JNK信号通路刺激AP-1活化。此外，我们发现IL-1还上调MMP-13的表达，并增强MMP介导的I型胶原降解。总的来说，这些结果表明，IL-1诱导MMP-9的表达激活AP-1通过ERK 1/2和JNK信号通路在成牙骨质细胞源性细胞系和MMP-13和MMP-9可能增强MMP介导的胶原降解。
It has been reported that matrix metalloproteinases (MMPs) are induced by many cytokines, and they are involved in various inflammatory processes, including periodontitis. However, the effects of interleukin-1 (IL-1) on MMP-9 expression in cementoblasts, the cells responsible for cementum production, remain largely unknown. In this study, we used qPCR and gelatin zymogram analysis to show that IL-1 upregulated MMP-9 expression in cementoblast-derived cell line. Several signaling pathways, such as ERK1/2, JNK, p38, and AP-1 (c-Fos and ATF-2), were activated in response to IL-1 stimulation. Furthermore, enhancement of AP-1 activity by IL-1 was further confirmed by the AP-1 reporter assay and the electrophoretic mobility shift assay (EMSA). Pretreatment with specific inhibitors of ERK1/2 (U0126), JNK (SP600125), and AP-1 (tanshinone IIA) attenuated IL-1-induced MMP-9 expression. In addition, inhibitors of ERK1/2 (U0126) and JNK (SP600125) attenuated IL-1-enhanced AP-1 activity. This suggested that IL-1 stimulated AP-1 activation, at least partially, through ERK1/2 and JNK signaling pathways. Moreover, we found that IL-1 also upregulated the expression of MMP-13 and enhanced MMP-mediated degradation of type I collagen. Collectively, these results suggested that IL-1 induced MMP-9 expression by activation of AP-1 through the ERK1/2 and JNK signaling pathways in cementoblast-derived cell line and enhanced MMP-mediated collagen degradation possibly by MMP-13 and MMP-9.