PMID- 27070823
OWN - NLM
STAT- MEDLINE
DCOM- 20170512
LR  - 20200204
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 186
IP  - 6
DP  - 2016 Jun
TI  - Nuclear Factor Erythroid 2-Related Factor 2 Down-Regulation in Oral Neutrophils 
      Is Associated with Periodontal Oxidative Damage and Severe Chronic Periodontitis.
PG  - 1417-26
LID - S0002-9440(16)30004-9 [pii]
LID - 10.1016/j.ajpath.2016.01.013 [doi]
AB  - 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.
CI  - Copyright (c) 2016 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Sima, Corneliu
AU  - Sima C
AD  - 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.
FAU - Aboodi, Guy M
AU  - Aboodi GM
AD  - Department of Periodontology, Faculty of Dentistry, University of Toronto, 
      Toronto, Ontario, Canada; Matrix Dynamics Group, Faculty of Dentistry, University 
      of Toronto, Toronto, Ontario, Canada.
FAU - Lakschevitz, Flavia S
AU  - Lakschevitz FS
AD  - Department of Periodontology, Faculty of Dentistry, University of Toronto, 
      Toronto, Ontario, Canada; Matrix Dynamics Group, Faculty of Dentistry, University 
      of Toronto, Toronto, Ontario, Canada.
FAU - Sun, Chunxiang
AU  - Sun C
AD  - Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, 
      Ontario, Canada.
FAU - Goldberg, Michael B
AU  - Goldberg MB
AD  - Department of Periodontology, Faculty of Dentistry, University of Toronto, 
      Toronto, Ontario, Canada.
FAU - Glogauer, Michael
AU  - Glogauer M
AD  - Department of Periodontology, Faculty of Dentistry, University of Toronto, 
      Toronto, Ontario, Canada; Matrix Dynamics Group, Faculty of Dentistry, University 
      of Toronto, Toronto, Ontario, Canada.
LA  - eng
GR  - K99 DE024575/DE/NIDCR NIH HHS/United States
GR  - R00 DE024575/DE/NIDCR NIH HHS/United States
GR  - TBO-122068/CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160409
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Nfe2l2 protein, mouse)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Blotting, Western
MH  - Chronic Periodontitis/*metabolism/*pathology
MH  - Down-Regulation
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Middle Aged
MH  - NF-E2-Related Factor 2/deficiency/*metabolism
MH  - Neutrophils/*metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Oxidative Stress/*physiology
MH  - Real-Time Polymerase Chain Reaction
PMC - PMC4901128
EDAT- 2016/04/14 06:00
MHDA- 2017/05/13 06:00
PMCR- 2017/06/01
CRDT- 2016/04/13 06:00
PHST- 2015/10/21 00:00 [received]
PHST- 2016/01/11 00:00 [revised]
PHST- 2016/01/19 00:00 [accepted]
PHST- 2016/04/13 06:00 [entrez]
PHST- 2016/04/14 06:00 [pubmed]
PHST- 2017/05/13 06:00 [medline]
PHST- 2017/06/01 00:00 [pmc-release]
AID - S0002-9440(16)30004-9 [pii]
AID - 10.1016/j.ajpath.2016.01.013 [doi]
PST - ppublish
SO  - Am J Pathol. 2016 Jun;186(6):1417-26. doi: 10.1016/j.ajpath.2016.01.013. Epub 
      2016 Apr 9.