Effects of Porphyromonas gingivalis LipopolysaccharideTolerized Monocytes on Inflammatory Responses in Neutrophils

• Published in: PloS one 2016-08, Vol.11 (8), p.e0161482-e0161482
• Main Authors: Zhu, Xiang-Qing, Lu, Wei, Chen, Yang, Cheng, Xiao-Fan, Qiu, Jia-Ying, Xu, Yan, Sun, Ying
• Format: Article
• Language: English
• Subjects: Apoptosis; Bacteria; Biology and Life Sciences; Caspase; Caspase-3; Cell Line; Cell Migration Assays, Leukocyte; Chemokines; Chemotactic response; Chemotaxis; Conditioning; Cytokines; Cytokines - metabolism; Endotoxins; Enzyme-linked immunosorbent assay; Gene expression; Gum disease; Homeostasis; Hospitals; Humans; Immunological tolerance; Inflammation - microbiology; Inflammation - physiopathology; Laboratories; Leukocyte migration; Leukocytes (neutrophilic); Lipopolysaccharides; Lipopolysaccharides - metabolism; Medicine and Health Sciences; Monocytes; Monocytes - physiology; Neutrophils; Neutrophils - physiology; Oral diseases; Oxygen; Periodontitis; Physiological aspects; Porphyromonas gingivalis; Porphyromonas gingivalis - physiology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Respiratory Burst; Risk factors; Trends; Virulence; Virulence factors; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0161482

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.