title: Nuclear Factor Erythroid 2-Related Factor 2 Down-Regulation in Oral Neutrophils Is Associated with Periodontal Oxidative Damage and Severe Chronic Periodontitis.
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.
authors.affiliation: Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, Massachusetts; Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts. Electronic address: csima@forsyth.org.
authors.forename: Corneliu
authors.initials: C
authors.lastname: Sima
authors.affiliation: Department of Periodontology, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada; Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Guy M
authors.initials: GM
authors.lastname: Aboodi
authors.affiliation: Department of Periodontology, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada; Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Flavia S
authors.initials: FS
authors.lastname: Lakschevitz
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Periodontology, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Goldberg
authors.affiliation: Department of Periodontology, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada; Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Glogauer
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D055113:Chronic Periodontitis / Q000378:metabolism* / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse