Beyond Toll-Like Receptors: Porphyromonas gingivalis Induces IL-6, IL-8, and VCAM-1 Expression Through NOD-Mediated NF-κB and ERK Signaling Pathways in Periodontal Fibroblasts
Beyond Toll-Like Receptors: Porphyromonas gingivalis Induces IL-6, IL-8, and VCAM-1 Expression Through NOD-Mediated NF-κB and ERK Signaling Pathways in Periodontal Fibroblasts
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DOI：
10.1007/s10753-013-9766-0
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发表时间：
2014-04-01
期刊：
影响因子：
5.1
通讯作者：
Ouyang, Xiangying
中科院分区：
文献类型：
--
作者：
Liu, Jianru;Wang, Yixiang;Ouyang, Xiangying
为了研究寡聚结构域（NODs）是否参与牙龈卟啉单胞菌诱导的白细胞介素(IL)-6、IL-8和血管细胞粘附分子(VCAM)-1在toll样受体（TLRs）外的表达，我们研究了NOD1/2在牙龈卟啉单胞菌诱导的人牙龈成纤维细胞（hGFs）和牙周韧带细胞（hpdlc）中IL-6、IL-8和VCAM-1表达中的作用。通过NODs的激活和沉默、电泳迁移率转移试验（EMSA）和途径阻断试验来探索其机制。结果显示，牙龈假单胞菌可诱导hGFs和hPDLs中NOD1、NOD2、IL-6、IL-8和VCAM-1 mRNA和蛋白水平的表达。激动剂激活NOD1/2可明显上调这些基因的表达，而沉默NOD1/2可显著减弱这些基因的表达。EMSA和NF-kappa B和细胞外信号调节激酶（ERK）1/2通路阻断实验也证实了这两条通路参与nod1 /2介导的IL-6、IL-8和VCAM-1的表达。总之，我们的研究结果表明，牙龈假单胞菌通过nod1 /2介导的nf - κ B和ERK1/2信号通路，介导hGFs和hpdlc中IL-6、IL-8和VCAM-1的表达。
To investigate whether oligomerization domains (NODs) are involved in Porphyromonas gingivalis-induced interleukin (IL)-6, IL-8, and vascular cell adhesion molecule (VCAM)-1 expression beyond Toll-like receptors (TLRs), we investigated the role of NOD1/2 in P. gingivalis-induced IL-6, IL-8, and VCAM-1 expression in human gingival fibroblasts (hGFs) and periodontal ligament cells (hPDLCs). The mechanism was explored by activation and silence of NODs, electrophoretic mobility shift assay (EMSA), and pathway blockade assays. Results showed that P. gingivalis could induce NOD1, NOD2, IL-6, IL-8, and VCAM-1 expression in hGFs and hPDLs at mRNA and protein levels. Activation of NOD1/2 by agonists could clearly upregulate the expression of these genes, while silence of NOD1/2 could remarkably attenuate them. EMSA and blockade of NF-kappa B and extracellular-signal-regulated kinase (ERK)1/2 pathway assays also verified that the two pathways were involved in NOD1/2-mediated IL-6, IL-8, and VCAM-1 expression. In conclusion, our findings demonstrated that P. gingivalis induced IL-6, IL-8, and VCAM-1 expression in hGFs and hPDLCs through NOD1/2-mediated NF-kappa B and ERK1/2 signaling pathways beyond TLRs.