title: Effects of Porphyromonas gingivalis LipopolysaccharideTolerized Monocytes on Inflammatory Responses in Neutrophils.
abstract: 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.
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.|Department of Periodontology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.|Department of Stomatology, Nanjing First Hospital, Nanjing, China.
authors.forename: Xiang-Qing
authors.initials: XQ
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.|Department of Periodontology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.|Department of Periodontology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.|Department of Periodontology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Cheng
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.|Department of Periodontology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Qiu
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.|Department of Periodontology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.|Department of Periodontology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D054441:Cell Migration Assays, Leukocyte; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000382:microbiology / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D016966:Porphyromonas gingivalis / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species