LPS from P. gingivalis and Hypoxia Increases Oxidative Stress in Periodontal Ligament Fibroblasts and Contributes to Periodontitis

Oxidative stress is characterized by an accumulation of reactive oxygen species (ROS) and plays a key role in the progression of inflammatory diseases. We hypothesize that hypoxic and inflammatory events induce oxidative stress in the periodontal ligament (PDL) by activating NOX4. Human primary PDL...

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Main Authors: L. Gölz, S. Memmert, B. Rath-Deschner, A. Jäger, T. Appel, G. Baumgarten, W. Götz, S. Frede
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2014/986264
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author L. Gölz
S. Memmert
B. Rath-Deschner
A. Jäger
T. Appel
G. Baumgarten
W. Götz
S. Frede
author_facet L. Gölz
S. Memmert
B. Rath-Deschner
A. Jäger
T. Appel
G. Baumgarten
W. Götz
S. Frede
author_sort L. Gölz
collection DOAJ
description Oxidative stress is characterized by an accumulation of reactive oxygen species (ROS) and plays a key role in the progression of inflammatory diseases. We hypothesize that hypoxic and inflammatory events induce oxidative stress in the periodontal ligament (PDL) by activating NOX4. Human primary PDL fibroblasts were stimulated with lipopolysaccharide from Porphyromonas gingivalis (LPS-PG), a periodontal pathogen bacterium under normoxic and hypoxic conditions. By quantitative PCR, immunoblot, immunostaining, and a specific ROS assay we determined the amount of NOX4, ROS, and several redox systems. Healthy and inflamed periodontal tissues were collected to evaluate NOX4 and redox systems by immunohistochemistry. We found significantly increased NOX4 levels after hypoxic or inflammatory stimulation in PDL cells (P<0.001) which was even more pronounced after combination of the stimuli. This was accompanied by a significant upregulation of ROS and catalase (P<0.001). However, prolonged incubation with both stimuli induced a reduction of catalase indicating a collapse of the protective machinery favoring ROS increase and the progression of inflammatory oral diseases. Analysis of inflamed tissues confirmed our hypothesis. In conclusion, we demonstrated that the interplay of NOX4 and redox systems is crucial for ROS formation which plays a pivotal role during oral diseases.
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series Mediators of Inflammation
spelling doaj-art-13345be424514ae4981d77fc1fd091c62025-02-03T06:42:26ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/986264986264LPS from P. gingivalis and Hypoxia Increases Oxidative Stress in Periodontal Ligament Fibroblasts and Contributes to PeriodontitisL. Gölz0S. Memmert1B. Rath-Deschner2A. Jäger3T. Appel4G. Baumgarten5W. Götz6S. Frede7Department of Orthodontics, Dental Clinic, University Hospital of Bonn, Welschnonnenstraße. 17, 53111 Bonn, GermanyDepartment of Orthodontics, Dental Clinic, University Hospital of Bonn, Welschnonnenstraße. 17, 53111 Bonn, GermanyDepartment of Orthodontics, Dental Clinic, University Hospital of Bonn, Welschnonnenstraße. 17, 53111 Bonn, GermanyDepartment of Orthodontics, Dental Clinic, University Hospital of Bonn, Welschnonnenstraße. 17, 53111 Bonn, GermanyCenter of Dento-Maxillo-Facial Medicine, Faculty of Medicine, University of Bonn, Welschnonnenstraße 17, 53111 Bonn, GermanyClinic of Anesthesiology and Intensive Care Medicine, University Hospital of Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, GermanyDepartment of Orthodontics, Dental Clinic, University Hospital of Bonn, Welschnonnenstraße. 17, 53111 Bonn, GermanyClinic of Anesthesiology and Intensive Care Medicine, University Hospital of Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, GermanyOxidative stress is characterized by an accumulation of reactive oxygen species (ROS) and plays a key role in the progression of inflammatory diseases. We hypothesize that hypoxic and inflammatory events induce oxidative stress in the periodontal ligament (PDL) by activating NOX4. Human primary PDL fibroblasts were stimulated with lipopolysaccharide from Porphyromonas gingivalis (LPS-PG), a periodontal pathogen bacterium under normoxic and hypoxic conditions. By quantitative PCR, immunoblot, immunostaining, and a specific ROS assay we determined the amount of NOX4, ROS, and several redox systems. Healthy and inflamed periodontal tissues were collected to evaluate NOX4 and redox systems by immunohistochemistry. We found significantly increased NOX4 levels after hypoxic or inflammatory stimulation in PDL cells (P<0.001) which was even more pronounced after combination of the stimuli. This was accompanied by a significant upregulation of ROS and catalase (P<0.001). However, prolonged incubation with both stimuli induced a reduction of catalase indicating a collapse of the protective machinery favoring ROS increase and the progression of inflammatory oral diseases. Analysis of inflamed tissues confirmed our hypothesis. In conclusion, we demonstrated that the interplay of NOX4 and redox systems is crucial for ROS formation which plays a pivotal role during oral diseases.http://dx.doi.org/10.1155/2014/986264
spellingShingle L. Gölz
S. Memmert
B. Rath-Deschner
A. Jäger
T. Appel
G. Baumgarten
W. Götz
S. Frede
LPS from P. gingivalis and Hypoxia Increases Oxidative Stress in Periodontal Ligament Fibroblasts and Contributes to Periodontitis
Mediators of Inflammation
title LPS from P. gingivalis and Hypoxia Increases Oxidative Stress in Periodontal Ligament Fibroblasts and Contributes to Periodontitis
title_full LPS from P. gingivalis and Hypoxia Increases Oxidative Stress in Periodontal Ligament Fibroblasts and Contributes to Periodontitis
title_fullStr LPS from P. gingivalis and Hypoxia Increases Oxidative Stress in Periodontal Ligament Fibroblasts and Contributes to Periodontitis
title_full_unstemmed LPS from P. gingivalis and Hypoxia Increases Oxidative Stress in Periodontal Ligament Fibroblasts and Contributes to Periodontitis
title_short LPS from P. gingivalis and Hypoxia Increases Oxidative Stress in Periodontal Ligament Fibroblasts and Contributes to Periodontitis
title_sort lps from p gingivalis and hypoxia increases oxidative stress in periodontal ligament fibroblasts and contributes to periodontitis
url http://dx.doi.org/10.1155/2014/986264
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