AI Article Synopsis
- Periodontitis is a chronic disease caused by bacteria, leading to a reduced immune response known as endotoxin tolerance when the host is exposed to bacterial components like lipopolysaccharide (LPS).
- In this study, researchers found that neutrophils exposed to supernatants from THP-1 cells treated with repeated doses of P. gingivalis LPS had reduced migration, higher reactive oxygen species (ROS) production, and lower apoptosis (Caspase 3 activity) compared to those exposed to supernatants from single treatment THP-1 cells.
- Additionally, a cytokine analysis revealed that tolerance in THP-1 cells resulted in decreased expression of several key cytokines, suggesting that these changes may
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990254 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161482 | PLOS |
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