Nuclear Factor Erythroid 2-Related Factor 2 Down-Regulation in Oral Neutrophils Is Associated with Periodontal Oxidative Damage and Severe Chronic Periodontitis

Corneliu Sima, Guy M. Aboodi, Flavia S. Lakschevitz, Chunxiang Sun, Michael B. Goldberg, Michael Glogauer

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1417-1426
Number of pages10
JournalAmerican Journal of Pathology
Volume186
Issue number6
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
Supported by Canadian Institute of Health Research grant TBO-122068 (M.G.) and National Institute of Dental and Craniofacial Research Award K99DE024575 (C.S.).

Publisher Copyright:
© 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

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