5-Aza-2′-deoxycytidine enhances lipopolysaccharide-induced inflammatory cytokine expression in human dental pulp cells by regulating TRAF6 methylation
5-Aza-2′-deoxycytidine enhances lipopolysaccharide-induced inflammatory cytokine expression in human dental pulp cells by regulating TRAF6 methylation
复制标题
5-Aza-2'-脱氧胞苷通过调节TRAF6甲基化增强脂多糖诱导的人牙髓细胞炎症细胞因子表达
DOI：
10.1080/21655979.2019.1621135
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发表时间：
2019-01-01
期刊：
影响因子：
4.9
通讯作者：
Xu, Qiong
中科院分区：
文献类型：
--
作者：
Feng, Zhihui;Zhan, Minkang;Xu, Qiong
牙髓炎症是一种常见的细菌驱动的炎症，其特征是炎症介质在人牙髓中局部积聚。 DNA甲基化是一种重要的表观遗传修饰，在基因转录中发挥着重要作用，其在炎症相关疾病中的作用最近引起了人们的关注。然而，人们对它在牙髓炎症中的作用知之甚少。本研究旨在阐明 DNA 甲基化在脂多糖 (LPS) 诱导的人牙髓细胞 (hDPC) 炎症反应中的作用。 hDPCs 用 DNA 甲基化抑制剂 5-aza-2MODIFIER LETTER PRIME-deoxycytidine (5-Aza-CdR) 预处理，并使用细胞因子抗体阵列检测 LPS 诱导的细胞因子表达。结果表明，5-Aza-CdR 显着增加了 LPS 处理细胞中几种促炎细胞因子的表达，包括 IL-6、IL-8、GM-CSF、MCP-2 和 RANTES。通过 qRT-PCR 和 ELISA 进一步验证了 IL-6 和 IL-8 表达水平的增加。此外，5-Aza-CdR 预处理导致 NK-kappa B 和 MAPK 途径中 p-IKK α/β、p-I kappa B α、p-p65 和 p-ERK 上调。此外，在 LPS 刺激的 hDPC 中进行 5-Aza-CdR 预处理后，TRAF6 启动子的 5mC 水平显着降低。研究结果表明，5-Aza-CdR 通过引起 hDPC 中 TRAF6 启动子中 5mc 水平下降，显着增强促炎细胞因子的表达并激活 NF-kappa B 和 MAPK 信号通路，这表明 DNA 甲基化可能在牙髓炎症中发挥重要作用。这项研究强调了 DNA 甲基化在牙髓感染免疫防御中的重要作用。[图表]。
Dental pulp inflammation is a common bacterially driven inflammation characterized by the local accumulation of inflammatory mediators in human dental pulp. DNA methylation is a crucial epigenetic modification that that plays a fundamental role in gene transcription, and its role in inflammation-related diseases has recently attracted attention. However, its role in dental pulp inflammation is poorly understood. This study is aimed to elucidate the role of DNA methylation in lipopolysaccharide (LPS)-induced inflammatory reaction in human dental pulp cells (hDPCs). hDPCs were pretreated with DNA methylation inhibitor 5-aza-2MODIFIER LETTER PRIME-deoxycytidine (5-Aza-CdR) and a cytokine antibody array was used to detect LPS-induced cytokine expression. The results indicated that 5-Aza-CdR significantly increased the expression of several pro-inflammatory cytokines in LPS-treated cells, including IL-6, IL-8, GM-CSF, MCP-2 and RANTES. The increased expression levels of IL-6 and IL-8 were further verified by qRT-PCR and ELISA. Furthermore, pretreatment with 5-Aza-CdR resulted in upregulation of p-IKK alpha/beta, p-I kappa B alpha, p-p65 and p-ERK in the NK-kappa B and MAPK pathways. In addition, the 5mC level of the TRAF6 promoter was significantly decreased following 5-Aza-CdR pretreatment in the LPS-stimulated hDPCs. The findings indicate that 5-Aza-CdR significantly enhances the expression of proinflammatory cytokines and activates the NF-kappa B and MAPK signaling pathways by eliciting a decline in the 5mc level in the TRAF6 promoter in hDPCs, suggesting that DNA methylation may play an important role in dental pulp inflammation. This study highlights the important role of DNA methylation in the immunity defense of dental pulp infection.[GRAPHICS].