P53 mediates lipopolysaccharide‐induced inflammation in human gingival fibroblasts

Liu, Jia; Zeng, Jiajun; Wang, Xiaoxuan; Zheng, Ming

doi:10.1002/jper.18-0026

Cited by 30 publications

(31 citation statements)

References 43 publications

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“…The present study observed that LPS stimulated the senescence process and SASP factors in gingival fibroblasts; following LPS stimulation, gingival fibroblasts exhibited a significant increase in the expression of p16, p53 and p21, as well as the secretion of IL-1β, IL-6 and TNF-α. These observations were consistent with a recent study, which showed that LPS increased secretion of IL-6 and TNF-α through p53-dependent activation (39).…”

Section: Discussionsupporting

confidence: 94%

Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression

Qin

Chen

et al. 2020

Int J Mol Med

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Overproduction of pro-inflammatory cytokines in the aged, which is called inflammaging, leads to the deterioration of periodontitis. Toll-like receptor 4 (TLR4) plays a role in the regulation of cellular senescence, and its expression increases with age. However, there has been limited research into the molecular mechanisms underlying the onset of periodontal inflammaging, and the interplay between TLR4 and inflammaging. In the present study, wild-type and TLR4 gene knockout mice were used to investigate the activation of the TLR4 pathway in mouse periodontitis and the expression of the nucleotide-binding and oligomerization domain-like receptor 3 (NLRP3) inflammasome, an upstream immune checkpoint during the development of inflammaging. Activation of TLR4 in a mouse model of periodontitis enhanced the expression of a senescence-associated secretory phenotype (SASP), which boosted the inflammaging process. Conversely, TLR4 activation downregulated the expression of B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and promoted the priming of NLRP3 inflammasome, both of which are regulators of SASP. Treating gingival fibroblasts with Bmi-1 inhibitor PTC209, it was demonstrated that TLR4 activated the NLRP3 pathway and the inflammaging process by suppressing Bmi-1. In addition, there was a significant reduction in the expression of Bmi-1 expression in the gingiva of patients with periodontitis compared with healthy controls. In conclusion, the present study demonstrated that TLR4 acted by inhibiting Bmi-1 to enhance the NLRP3 pathway and SASP factors. This cascade of reactions may contribute to the senescence of the periodontium.

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Section: Discussionsupporting

confidence: 94%

Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression

Qin

Chen

et al. 2020

Int J Mol Med

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“…Generally, in cells and tissue oxidative stress can incite inflammation, and excess inflammation can also cause oxidative stress, leading to excessive cell and tissue damage (Rimessi, Previati, Nigro, Wieckowski, & Pinton, 2016). Luan's group proposed that in human gingival fibroblasts, the inflammatory cytokines induced by lipopolysaccharide stimulation were modulated by the interaction between P53 and mitochondrial ROS (mtROS) in the context of mitochondrial dysfunction (Liu, Zeng, Wang, Zheng, & Luan, 2018). Damaged mitochondria can also release mitochondrial DNA, which could be another source leading to inflammation.…”

Section: Discussionmentioning

confidence: 99%

Activation of mitophagy in inflamed odontoblasts

Yang

Duan

et al. 2019

Oral Diseases

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Objectives Mitophagy is an important mitochondrial quality control mechanism. In this study, we investigated the mitochondrial damage and mitophagy occurred in inflammatory human dental pulp and lipopolysaccharide‐stimulated preodontoblasts. Materials and Methods In dental pulp tissues and lipopolysaccharide‐stimulated preodontoblasts, immunofluorescences and Western blot were performed to detect the expression of mitochondrial and mitophagy‐related proteins, and autophagy markers were also examined. Reactive oxygen species generated by mitochondria were examined by MitoSOX. Transmission electron microscope (TEM) was used to examine the morphology of mitochondria in lipopolysaccharide‐stimulated preodontoblasts. Results The active fission activity of mitochondria and mitophagy in inflammatory dental pulp was observed. In lipopolysaccharide‐treated preodontoblasts, mitophagy‐related proteins were also upregulated. Moreover, increased reactive oxygen species in the inflamed preodontoblasts were observed. Additionally, single‐membrane autolysosomes containing partially degraded mitochondria with swollen inner membranes in lipopolysaccharide‐treated preodontoblasts were observed by TEM. Conclusions These results indicate that mitochondria were damaged and mitophagy might be activated to degrade impaired mitochondria in inflamed odontoblasts.

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“…For example, Li, Pedro Bullón, and Kiran Napa et al believe that the treatment of fibroblast with P . gingivalis LPS leads to increased mtROS production, loss of MMP, reduced oxygen consumption, and mitochondrial biogenesis, 42 – 46 and Zhu et al obtained similar results in human gingival epithelial cells. The authors concluded that the ROS levels were increased significantly in cells treated with both high glucose and P .…”

Section: Discussionmentioning

confidence: 74%

Porphyromonas gingivalis infection promotes mitochondrial dysfunction through Drp1-dependent mitochondrial fission in endothelial cells

Dong

Ying

et al. 2021

Int J Oral Sci

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Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis, has been shown to accelerate the progression of atherosclerosis (AS). However, the definite mechanisms remain elusive. Emerging evidence supports an association between mitochondrial dysfunction and AS. In our study, the impact of P. gingivalis on mitochondrial dysfunction and the potential mechanism were investigated. The mitochondrial morphology of EA.hy926 cells infected with P. gingivalis was assessed by transmission electron microscopy, mitochondrial staining, and quantitative analysis of the mitochondrial network. Fluorescence staining and flow cytometry analysis were performed to determine mitochondrial reactive oxygen species (mtROS) and mitochondrial membrane potential (MMP) levels. Cellular ATP production was examined by a luminescence assay kit. The expression of key fusion and fission proteins was evaluated by western blot and immunofluorescence. Mdivi-1, a specific Drp1 inhibitor, was used to elucidate the role of Drp1 in mitochondrial dysfunction. Our findings showed that P. gingivalis infection induced mitochondrial fragmentation, increased the mtROS levels, and decreased the MMP and ATP concentration in vascular endothelial cells. We observed upregulation of Drp1 (Ser616) phosphorylation and translocation of Drp1 to mitochondria. Mdivi-1 blocked the mitochondrial fragmentation and dysfunction induced by P. gingivalis. Collectively, these results revealed that P. gingivalis infection promoted mitochondrial fragmentation and dysfunction, which was dependent on Drp1. Mitochondrial dysfunction may represent the mechanism by which P. gingivalis exacerbates atherosclerotic lesions.

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P53 mediates lipopolysaccharide‐induced inflammation in human gingival fibroblasts

Cited by 30 publications

References 43 publications

Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression

Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression

Activation of mitophagy in inflamed odontoblasts

Porphyromonas gingivalis infection promotes mitochondrial dysfunction through Drp1-dependent mitochondrial fission in endothelial cells

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