Abstract
Reactive oxygen species (ROS) production is an antimicrobial response to pathogenic challenge that may, in the case of persistent infection, have deleterious effects on the tissue of origin. A rat periodontal disease model was used to study ROS-induced chronic epithelial inflammation and bone loss. Lipopolysaccharide (LPS) was applied for 8 weeks into the gingival sulcus, and histological analysis confirmed the onset of chronic disease. Junctional epithelium was collected from healthy and diseased animals using laser-capture microdissection, and expression microarray analysis was performed. Of 19,730 genes changed in disease, 42 were up-regulated ≥4-fold. Three of the top 10 LPS-induced genes, monoamine oxidase B (MAO/B) and flavin-containing monooxygenase 1 and 2, are implicated in ROS signaling. LPSassociated induction of the ROS mediator H2O2, as well as MAO/B and tumor necrosis factor (TNF)-α levels were validated in the rat histological sections and a porcine junctional epithelial cell culture model. Topical MAO inhibitors significantly counteracted LPS-associated elevation of H 2O2 production and TNF-α expression in vivo and in vitro, inhibited disease-associated apical migration and proliferation of junctional epithelium and inhibited induced systemic H2O2 levels and alveolar bone loss in vivo. These results suggest that LPS induces chronic wounds via elevated MAO/B-mediated increases in H2O 2 and TNF-α activity by epithelial cells and is further associated with more distant effects on systemic oxidative stress and alveolar bone loss.
| Original language | English |
|---|---|
| Pages (from-to) | 1398-1409 |
| Number of pages | 12 |
| Journal | American Journal of Pathology |
| Volume | 175 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2009 |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
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Lipopolysaccharide-induced epithelial monoamine oxidase mediates alveolar bone loss in a rat chronic wound model. / Ekuni, Daisuke; Firth, James D.; Nayer, Tarun; Tomofuji, Takaaki; Sanbe, Toshihiro; Irie, Koichiro; Yamamoto, Tatsuo; Oka, Takashi; Liu, Zhenzi; Vielkind, Juergen; Putnins, Edward E.
In: American Journal of Pathology, Vol. 175, No. 4, 2009, p. 1398-1409.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lipopolysaccharide-induced epithelial monoamine oxidase mediates alveolar bone loss in a rat chronic wound model
AU - Ekuni, Daisuke
AU - Firth, James D.
AU - Nayer, Tarun
AU - Tomofuji, Takaaki
AU - Sanbe, Toshihiro
AU - Irie, Koichiro
AU - Yamamoto, Tatsuo
AU - Oka, Takashi
AU - Liu, Zhenzi
AU - Vielkind, Juergen
AU - Putnins, Edward E.
PY - 2009
Y1 - 2009
N2 - Reactive oxygen species (ROS) production is an antimicrobial response to pathogenic challenge that may, in the case of persistent infection, have deleterious effects on the tissue of origin. A rat periodontal disease model was used to study ROS-induced chronic epithelial inflammation and bone loss. Lipopolysaccharide (LPS) was applied for 8 weeks into the gingival sulcus, and histological analysis confirmed the onset of chronic disease. Junctional epithelium was collected from healthy and diseased animals using laser-capture microdissection, and expression microarray analysis was performed. Of 19,730 genes changed in disease, 42 were up-regulated ≥4-fold. Three of the top 10 LPS-induced genes, monoamine oxidase B (MAO/B) and flavin-containing monooxygenase 1 and 2, are implicated in ROS signaling. LPSassociated induction of the ROS mediator H2O2, as well as MAO/B and tumor necrosis factor (TNF)-α levels were validated in the rat histological sections and a porcine junctional epithelial cell culture model. Topical MAO inhibitors significantly counteracted LPS-associated elevation of H 2O2 production and TNF-α expression in vivo and in vitro, inhibited disease-associated apical migration and proliferation of junctional epithelium and inhibited induced systemic H2O2 levels and alveolar bone loss in vivo. These results suggest that LPS induces chronic wounds via elevated MAO/B-mediated increases in H2O 2 and TNF-α activity by epithelial cells and is further associated with more distant effects on systemic oxidative stress and alveolar bone loss.
AB - Reactive oxygen species (ROS) production is an antimicrobial response to pathogenic challenge that may, in the case of persistent infection, have deleterious effects on the tissue of origin. A rat periodontal disease model was used to study ROS-induced chronic epithelial inflammation and bone loss. Lipopolysaccharide (LPS) was applied for 8 weeks into the gingival sulcus, and histological analysis confirmed the onset of chronic disease. Junctional epithelium was collected from healthy and diseased animals using laser-capture microdissection, and expression microarray analysis was performed. Of 19,730 genes changed in disease, 42 were up-regulated ≥4-fold. Three of the top 10 LPS-induced genes, monoamine oxidase B (MAO/B) and flavin-containing monooxygenase 1 and 2, are implicated in ROS signaling. LPSassociated induction of the ROS mediator H2O2, as well as MAO/B and tumor necrosis factor (TNF)-α levels were validated in the rat histological sections and a porcine junctional epithelial cell culture model. Topical MAO inhibitors significantly counteracted LPS-associated elevation of H 2O2 production and TNF-α expression in vivo and in vitro, inhibited disease-associated apical migration and proliferation of junctional epithelium and inhibited induced systemic H2O2 levels and alveolar bone loss in vivo. These results suggest that LPS induces chronic wounds via elevated MAO/B-mediated increases in H2O 2 and TNF-α activity by epithelial cells and is further associated with more distant effects on systemic oxidative stress and alveolar bone loss.
UR - http://www.scopus.com/inward/record.url?scp=73549104086&partnerID=8YFLogxK
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U2 - 10.2353/ajpath.2009.090108
DO - 10.2353/ajpath.2009.090108
M3 - Article
C2 - 19779138
AN - SCOPUS:73549104086
VL - 175
SP - 1398
EP - 1409
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 4
ER -