Nuclear Factor Erythroid 2-Related Factor 2 Down-Regulation in Oral Neutrophils Is Associated with Periodontal Oxidative Damage and Severe Chronic Periodontitis
Nuclear Factor Erythroid 2-Related Factor 2 Down-Regulation in Oral Neutrophils Is Associated with Periodontal Oxidative Damage and Severe Chronic Periodontitis
复制标题
口腔中性粒细胞核因子-红细胞相关因子2表达下调与牙周组织氧化损伤及重度慢性牙周炎的关系
DOI：
10.1016/j.ajpath.2016.01.013
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发表时间：
2016-06-01
影响因子：
6
通讯作者：
Glogauer, Michael
中科院分区：
文献类型：
--
作者：
Sima, Corneliu;Aboodi, Guy M.;Glogauer, Michael
活性氧和抗氧化剂之间的平衡在牙周健康中起着重要作用。我们之前已经证明，在常规治疗难治性慢性牙周炎（CP）患者中，口服多形核中性粒细胞（oPMNs）产生的高活性氧与牙周组织的严重破坏有关。本研究表明，尽管在口腔中募集增强，但通过下调oPMN中核因子红系2相关因子2 （Nrf2）通路抑制抗氧化剂产生与严重CP有关。患病患者PMNs中，Nrf2介导的氧化应激反应通路中有24个基因下调。Nrf2下游的oPMN超氧化物歧化酶1和过氧化氢酶水平在严重CP中降低，尽管招募增加。与野生型相比，Nrf2（-/-）小鼠对牙周炎诱导的牙龈下结扎反应有更严重的牙周组织损失。Nrf2（-/-）小鼠牙周病变中8-羟基脱氧鸟苷水平升高，表明氧化损伤程度高。我们首次报道了严重CP患者的oPMNs Nrf2通路下调。CP患者的PMNs可能在口腔内高募集的背景下引发低抗氧化反应，导致氧化组织损伤增加。
The balance between reactive oxygen species and antioxidants plays an important role in periodontal health. We previously demonstrated that high reactive oxygen species production by oral polymorphonuclear neutrophils (oPMNs) in chronic periodontitis (CP) refractory to conventional therapy is associated with severe destruction of periodontium. Herein, we show that inhibition of antioxidant production through down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in oPMN, despite enhanced recruitment in the oral cavity, is associated with severe CP. Twenty-four genes in the Nrf2-mediated oxidative stress response pathway were down-regulated in PMNs of diseased patients. Downstream of Nrf2, levels of oPMN superoxide dismutase 1 and catalase were decreased in severe CP, despite increased recruitment. Nrf2(-/-) mice had more severe loss of periodontium in response to periodontitis-inducing subgingival ligatures compared with wild-types. Levels of 8-hydroxy-deoxyguanosine were increased in periodontal Lesions of Nrf2(-/-) mice, indicating high oxidative damage. We report, for the first time, Nrf2 pathway down-regulation in oPMNs of patients with severe CP. PMNs of CP patients may be primed for low antioxidant response in the context of high recruitment in the oral cavity, resulting in increased oxidative tissue damage.