Department of Periodontology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Oral Dis. 2018 Nov;24(8):1572-1580. doi: 10.1111/odi.12933. Epub 2018 Aug 14.
Periodontitis is a highly prevalent chronic inflammatory disease that results in destruction of tooth-supporting structures followed by tooth-loss. Until now, periodontitis has been regarded to be initiated by bacterial infection followed by aberrant host response. Although increasing evidence suggests a strong association between oxidative stress and periodontitis, precise molecular mechanism has been left unanswered. In this study, we investigated roles of SOD2, the main antioxidant enzyme maintaining reactive oxygen species (ROS) homeostasis, under inflammatory conditions.
We computationally analyzed SOD2 expression in periodontitis. To confirm this data, immunoblot assay was performed with samples from periodontitis patients. The cellular mechanism of change in SOD2 expression was identified through immunoblot assay and immunofluorescence. To evaluate the molecular function of SOD2, we generated SOD2-deficient cells by utilizing the CRISPR/Cas9 system.
We first determined that SOD2 expression was significantly increased in periodontitis. We also confirmed that SOD2 expression was upregulated through the NF-κB pathway when the inflammatory signal was stronger and extended. Gene manipulation against SOD2 through the CRISPR/Cas9 system showed that the absence of SOD2 increased production of NLRP3 inflammasome components.
Our study demonstrates that intracellular SOD2 has a protective role by suppressing NLRP inflammasome-caspase-1-IL-1β axis under inflammatory conditions.
牙周炎是一种高度流行的慢性炎症性疾病,可导致支持牙齿的结构破坏,进而导致牙齿缺失。到目前为止,牙周炎被认为是由细菌感染引发的,随后是异常的宿主反应。尽管越来越多的证据表明氧化应激与牙周炎之间存在很强的关联,但确切的分子机制尚未得到解答。在这项研究中,我们研究了在炎症条件下维持活性氧(ROS)稳态的主要抗氧化酶 SOD2 的作用。
我们通过计算分析了牙周炎中 SOD2 的表达。为了证实这一数据,我们用牙周炎患者的样本进行了免疫印迹分析。通过免疫印迹分析和免疫荧光,确定了 SOD2 表达变化的细胞机制。为了评估 SOD2 的分子功能,我们利用 CRISPR/Cas9 系统生成了 SOD2 缺陷细胞。
我们首先确定 SOD2 的表达在牙周炎中显著增加。我们还证实,当炎症信号更强且持续时,SOD2 的表达通过 NF-κB 途径上调。通过 CRISPR/Cas9 系统对 SOD2 进行基因操作表明,SOD2 的缺失会增加 NLRP3 炎性小体成分的产生。
我们的研究表明,在炎症条件下,细胞内 SOD2 通过抑制 NLRP 炎性小体-半胱天冬酶-1-IL-1β 轴发挥保护作用。