LPS from P. gingivalis Negatively Alters Gingival Cell Mitochondrial Bioenergetics

Abstract

Objective Oral inflammatory pathologies are linked to increased oxidative stress, thereby partly explaining their relevance in the etiology of systemic disorders. The purpose of this work was to determine the degree to which LPS from Porphyromonas gingivalis, the primary pathogen related to oral inflammation, altered gingival mitochondrial function and reactive oxygen species generation. Methods Human gingival fibroblast (HGF-1) cells were treated with lipopolysaccharide of P. gingivalis. Mitochondrial function was determined via high-resolution respirometry. P. gingivalisMitochondrial function was determined via high-resolution respirometry. Results LPS-treated HGF-1 cells had significantly higher mitochondrial complex IV and higher rates of mitochondrial respiration. However, this failed to translate into greater ATP production, as ATP production was paradoxically diminished with LPS treatment. Nevertheless, production of the reactive H2O2 was elevated with LPS treatment. Conclusions LPS elicits an increase in gingival cell mitochondria content, with a subsequent increase in reactive oxygen species production (i.e., H2O2), despite a paradoxical reduction in ATP generation. These findings provide an insight into the nature of oxidative stress in oral inflammatory pathologies.

<p>Eldecalcitol Inhibits LPS-Induced NLRP3 Inflammasome-Dependent Pyroptosis in Human Gingival Fibroblasts by Activating the Nrf2/HO-1 Signaling Pathway</p>

“…Therefore, the determination of H 2 O 2 content is of great significance for further revealing whether cells are in a state of oxidative stress. 40 Based on these studies, our study shows that LPS can interact with TLR4 and then induce the accumulation of total intracellular ROS, H 2 O 2 , and the NLRP3 inflammasome relative proteins and caspase-1 p20 in a dose-dependent manner, and further that the ROS inhibitor NAC can inhibit the activation of NLRP3 inflammasomes. These experimental data fully verify that the generation of oxidative stress is an important change in human gingival fibroblasts induced by LPS while further demonstrating that its consequence is pyroptosis.…”

A GGT Inhibitor Suppresses IL-6 and IL-8 Expressions Enhanced by LPS in Gingival Fibroblasts

“…It is essential to accelerate differentiation into epithelial cells for repair (19) , and epithelial growth factors produced by the connective tissues assist in this process (20) . (24) and signal transduction via p38 MAPK pathway with apoptosis signalregulating kinase 1 (ASK1) (25 -28) was impaired, causing decreased IL -6 and IL -8 expression. GGsTop ® might indirectly suppress ROS production via maintaining intracellular GSH which has antioxidant effect.…”

Poor Oral Health as a Determinant of Malnutrition and Sarcopenia

“…Interestingly, poor oral health may predispose one to a chronic low-grade inflammatory state through periodontal disease, which is a well-known risk factor for frailty and sarcopenia [25,128,129]. In fact, the detrimental effects of periodontitis are not confined solely to the oral cavity, but extend systemically, leading to metabolic alterations [130], including insulin resistance [131], diabetes [131,132], arthritis [133], and heart disease [134]. Furthermore, alterations in mitochondrial function leading to oxidative stress through the production of reactive oxygen species (ROS) have also been reported to mediate both oral and systemic pathologies (i.e., sarcopenia) [108,[135][136][137].…”