Mitochondrial reactive oxygen species mediate the lipopolysaccharide-induced pro-inflammatory response in human gingival fibroblasts
Mitochondrial reactive oxygen species mediate the lipopolysaccharide-induced pro-inflammatory response in human gingival fibroblasts
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线粒体活性氧介导脂多糖诱导的人牙龈成纤维细胞的促炎反应
DOI：
10.1016/j.yexcr.2016.08.007
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发表时间：
2016-09-10
影响因子：
3.7
通讯作者：
Luan, Qing Xian
中科院分区：
文献类型：
--
作者：
Li, Xue;Wang, Xiaoxuan;Luan, Qing Xian
虽然牙周病是由寄居在牙齿表面和牙龈沟的细菌引起的，但宿主的反应被认为在结缔组织和骨骼的破坏中起着重要作用。线粒体活性氧（mtROS）已被提出通过先天免疫系统调节炎症反应的激活。然而，mtROS在调节人牙龈成纤维细胞（HGFs）对脂多糖（LPS）免疫刺激的反应中的作用尚未完全阐明。在这里，我们发现来自牙龈卟啉单胞菌的LPS刺激HGFs增加mtROS的产生，这可以通过线粒体靶向外源性抗氧化剂（mito-TEMPO）处理或转染锰超氧化物歧化酶（MnSOD）来抑制。一项时间过程研究显示，在hgf中，mtROS浓度的增加先于炎症细胞因子的表达。Mito-TEMPO处理或MnSOD转染也能显著阻止lps诱导的白细胞介素(IL)-1 β、IL-6和肿瘤坏死因子α的升高。此外，抑制lps诱导的mtROS生成抑制了p38、c-Jun n端激酶和核因子κ B激酶抑制剂的激活以及核因子κ B的核定位。这些结果表明，mtROS生成是lps诱导的hgf促炎反应的关键信号事件。(C) 2016 Elsevier Inc.版权所有。
Although periodontal diseases are initiated by bacteria that colonize the tooth surface and gingival sulcus, the host response is believed to play an essential role in the breakdown of connective tissue and bone. Mitochondrial reactive oxygen species (mtROS) have been proposed to regulate the activation of the inflammatory response by the innate immune system. However, the role of mtROS in modulating the response of human gingival fibroblasts (HGFs) to immune stimulation by lipopolysaccharides (LPS) has yet to be fully elucidated. Here, we showed that LPS from Porphyromonas gingivalis stimulated HGFs to increase mtROS production, which could be inhibited by treatment with a mitochondrial-targeted exogenous antioxidant (mito-TEMPO) or transfection with manganese superoxide dismutase (MnSOD). A time-course study revealed that an increase in the concentration of mtROS preceded the expression of inflammatory cytokines in HGFs. Mito-TEMPO treatment or MnSOD transfection also significantly prevented the LPS-induced increase of interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha. Furthermore, suppressing LPS-induced mtROS generation inhibited the activation of p38, c-Jun N-terminal kinase, and inhibitor of nuclear factor-kappa B kinase, as well as the nuclear localization of nuclear factor-kappa B. These results demonstrate that mtROS generation is a key signaling event in the LPS-induced pro-inflammatory response of HGFs. (C) 2016 Elsevier Inc. All rights reserved.