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Nuclear Factor Erythroid 2-Related Factor 2 Down-Regulation in Oral Neutrophils
Is Associated with Periodontal Oxidative Damage and Severe Chronic Periodontitis
#MMPMID27070823
Sima C
; Aboodi GM
; Lakschevitz FS
; Sun C
; Goldberg MB
; Glogauer M
Am J Pathol
2016[Jun]; 186
(6
): 1417-26
PMID27070823
show ga
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.
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