Effects of Porphyromonas gingivalis LipopolysaccharideTolerized Monocytes on Inflammatory Responses in Neutrophils

Periodontitis is a chronic inflammatory disease induced by bacteria. Exposure of the host to periodontal pathogens and their virulence factors induces a state of hyporesponsiveness to subsequent stimulations, which is termed endotoxin tolerance. The role and mechanism of lipopolysaccharide (LPS)-tol...

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Published inPloS one Vol. 11; no. 8; p. e0161482
Main Authors Zhu, Xiang-Qing, Lu, Wei, Chen, Yang, Cheng, Xiao-Fan, Qiu, Jia-Ying, Xu, Yan, Sun, Ying
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 18.08.2016
Public Library of Science (PLoS)
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Summary:Periodontitis is a chronic inflammatory disease induced by bacteria. Exposure of the host to periodontal pathogens and their virulence factors induces a state of hyporesponsiveness to subsequent stimulations, which is termed endotoxin tolerance. The role and mechanism of lipopolysaccharide (LPS)-tolerized monocytes in inflammatory responses in neutrophils are currently unclear. Here, conditioned supernatants were collected from THP-1 cells treated with or without repeated 1 μg/ml Porphyromonas gingivalis (P.gingivalis) LPS. The chemotactic response of freshly isolated neutrophils recruited by supernatants was determined by a transwell migration assay, which demonstrated a reduced migration of neutrophils stimulated with supernatants from tolerized THP-1 cells in comparison to non-tolerized THP-1 cells. In addition, there was a marked increase in reactive oxygen species (ROS) generation and a significant decrease in Caspase 3 activities in neutrophils treated with supernatants from THP-1 cells that were treated repeatedly with P.gingivalis LPS in comparison to single treatment. A cytokine antibody array was then used to assess cytokine expression patterns in THP-1 cells. In tolerized THP-1 cells, 43 cytokine (43/170) expression levels were decreased, including chemokine ligand 23 (CCL23) and IFN-γ, while 11 cytokine (11/170) expression levels were increased, such as death receptor 6 (DR6). Furthermore, there was decreased production of IFN-γ and epithelial neutrophil activating peptide-78 (ENA-78) in THP-1 cells after stimulation with repeated P. gingivalis LPS in comparison to single challenge, which was confirmed by ELISA. Therefore, P.gingivalis LPS- tolerized THP-1 cells were able to depress neutrophil chemotaxis and apoptosis, and contribute to respiratory burst, which might be related to the changes in cytokine expression patterns in THP-1 cells.
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Competing Interests: The authors have declared that no competing interests exist.
Conceptualization: YS. Data curation: XQZ WL. Formal analysis: XQZ WL YS. Funding acquisition: YS. Investigation: XQZ WL YC XFC JYQ. Methodology: YS. Project administration: YS. Resources: YX. Supervision: YS. Validation: XQZ WL YC XFC JYQ. Visualization: XQZ WL YS. Writing - original draft: XQZ WL. Writing - review & editing: YS.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0161482