Liu 2018 J Periodontol
|Liu J, Zeng J, Wang X, Zheng M, Luan Q (2018) P53 mediates lipopolysaccharide-induced inflammation in human gingival fibroblasts. J Periodontol [Epub ahead of print].|
Abstract: The role of reactive oxygen species (ROS) in activation of the inflammatory response has been proven in previous study using human gingival fibroblasts (HGFs) to lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg) stimulation, but its exact mechanism has not been established. ROS can be generated through increased oxidative phosphorylation. P53 originally identified as a tumor suppressor, has been demonstrated to be associated with energy metabolism. We proposed that LPS-induced inflammatory cytokines release in HGFs is mediated by interaction between P53 and ROS levels.
HGFs were grown in medium with Pg LPS stimulation. Gene expression was performed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. HGFs were also processed by immunofluorescence to characterize the localization of P53. ROS was measured using a multimodal microplate reader and immunofluorescence microscopy. Cellular respiration levels were performed with a high-resolution respirometer. Cytokines secretion was confirmed by enzyme-linked immunosorbent assay.
LPS-induced P53 activity and localization in mitochondria led to cellular redox imbalance and mitochondrial dysfunction, thus triggered the cellular inflammatory response with increased secretion of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. Furthermore, the cellular redox imbalance and inflammation induced by LPS were reversed by inhibiting P53 activity. P53 expression followed by LPS-induced inflammation was also be restricted by suppressing ROS generation.
The present study shows that LPS-induced inflammation in HGFs is partially dependent on P53 modulating ROS and ROS stimulating P53, which suggests that P53 and ROS may form a feedback loop. The identification of this mechanism may provide potential new therapeutic strategies for periodontitis.
© 2018 American Academy of Periodontology.
• Keywords: Cell biology, Cytokines, Fibroblasts, Oxidative stress, Periodontitis, Reactive oxygen species (ROS) • Bioblast editor: Plangger M
Labels: MiParea: Respiration
Organism: Human Tissue;cell: Fibroblast Preparation: Intact cells
Coupling state: LEAK, ET Pathway: ROX HRR: Oxygraph-2k