Expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 6 in human dental pulp tissues and cells

Zhao, Yiming; Shen, Zhen; Li, Junda; Huang, Shuheng; Wang, Runfu; Zhao, Lin; Song, Zhenyuan

doi:10.1016/j.archoralbio.2020.104794

Cited by 4 publications

(4 citation statements)

References 32 publications

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“…LPS also stimulates NLRP6 expression and its knock-down decreases IL-1β production [ 99 ]. Lipopolysaccharide also upregulates both C5a and C5aR (parts of the complement system) mRNA especially on the second day post-stimulation [ 100 ].…”

Section: Resultsmentioning

confidence: 99%

Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis—A Systematic Review

et al. 2022

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Lipopolysaccharide (LPS) is widely used for induction of inflammation in various human tissues, including dental pulp. The purpose of this study was to summarize current medical literature focusing on (1) cell types used by researchers to simulate dental pulp inflammation, (2) LPS variants utilized in experimental settings and how these choices affect the findings. Our study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched for studies reporting outcomes of lipopolysaccharide application on dental pulp cells in vitro using electronic databases: MEDLINE, Web of Science and Scopus. Having gathered data from 115 papers, we aimed to present all known effects LPS has on different cell types present in dental pulp. We focused on specific receptors and particles that are involved in molecular pathways. Our review provides an essential foundation for further research using in vitro models of pulpitis.

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Section: Resultsmentioning

confidence: 99%

Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis—A Systematic Review

et al. 2022

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“…In human periodontal ligament cells, NLRP6 was found to suppresses LPS induced NF-jB activation and IL-1b upregulation (Lu et al 2019). Whereas in HDPCs, NLRP6 was found to promote IL-1b upregulation by LPS (Zhao et al 2020). The inconsistency of the function of NLRP6 in these studies remains unknown.…”

Section: Discussionmentioning

confidence: 97%

“…Whereas in HDPCs, NLRP6 was found to promote IL‐1β upregulation by LPS (Zhao et al . 2020). The inconsistency of the function of NLRP6 in these studies remains unknown.…”

Section: Discussionmentioning

confidence: 99%

NLRP6‐caspase 4 inflammasome activation in response to cariogenic bacterial lipoteichoic acid in human dental pulp inflammation

Tian

Liu

et al. 2021

Int Endodontic J

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Aim To explore the presence and function of NLRP6‐caspase 4 inflammasome in human pulp tissue and human dental pulp cells (HDPCs). Methodology Pulp tissue was collected from freshly extracted human caries‐free third molars and third molars with irreversible pulpitis. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot were performed to assess the expression of NLRP6‐caspase 4 inflammasome. HDPCs were prepared from normal human pulp tissues and challenged with Porphyromonas gingivalis LPS. Enzyme‐linked immunosorbent assay (ELISA) and qRT‐PCR were performed to assess if LPS can upregulate NLRP6 and caspase‐4. HDPCs were further challenged with LPS followed with cytosolic Streptococcus mutans lipoteichoic acid (LTA). SiRNA targeting NLRP6 and Casp4 and pharmacology inhibitor Ac‐FLTD‐CMK and MCC950 were used to assess if Streptococcus mutans LTA can activate the NLRP6 but not the NLRP3 inflammasome. Western blot and ELISA were performed to evaluate inflammasome activation. The Student’s t‐test and one‐way anova were used for statistical analysis. Results NLRP6‐caspase 4 inflammasome was upregulated and activated in inflamed human dental pulp tissue. In HDPCs, Porphyromonas gingivalis LPS upregulated the expression of NLRP6, CASP1 and CASP4 in a type I interferon dependent manner. After LPS priming, cytosolic Streptococcus mutans LTA triggered NLRP6‐caspase 4 inflammasome activation. Knockdown of NLRP6 or CASP4 using siRNA or using pharmacology inhibitor Ac‐FLTD‐CMK but not MCC950 efficiently suppressed inflammasome activation by cytosolic LTA. Conclusions NLRP6‐caspase 4 inflammasome may play an important role in pulp inflammation and immune defence. Inflammatory caspases represent a pharmacological target to restrain pulpal inflammation.

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“…The cells in the pulp–dentine complex are equipped with pattern recognition receptors to detect pathogen‐associated molecular patterns (PAMP) from invading bacteria. Multiple receptors, including Toll‐like receptors 2 and 4, nucleotide‐binding oligomerization domain (NOD) proteins 1 and 2, as well as inflammasome forming NOD‐like receptor family member pyrin domain containing 3 and 6, are present in the pulp (Hahn & Liewehr, 2007; Hosoya & Matsushima, 1997; Song et al, 2012; Tian et al, 2020; Tokuda et al, 2001; Zhao et al, 2020). Upon detecting the corresponding bacterial motif, the pulp cells initiate the inflammatory cascade aiming at containing, and ultimately eradicating, the infection (Cooper et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐4691‐3p inhibits the inflammatory response by targeting STING in human dental pulp cells: A laboratory investigation

et al. 2023

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AimThe regulation of human dental pulp inflammation is not fully understood. This study aims to investigate the effect of miR‐4691‐3p on the cGAS‐STING signaling cascade and its downstream cytokines production in human dental pulp cells (HDPCs)MethodologyNormal dental pulp tissue and pulp tissue with irreversible pulpitis from third molars were collected. HDPCswere isolated from pulp tissue. The expression of STING mRNA and miR‐4691‐3p was measured by quantitative real‐time PCR (qRT‐PCR). Bioinformatic computation via TargetScanHuman 8.0 and a luciferase reporter assay was used to identify the targets of miR‐4691‐3p. A miR‐4691‐3p mimic and inhibitor were used to upregulate or downregulate miR‐4691‐3p expression in HDPCs. HDPCs were transfected with c‐di‐AMP, c‐di‐GMP, cGAMP, interferon stimulatory DNA (ISD), bacterial genomic DNA. Immunoblot was performed to detect the phosphorylation of TBK1, p65, and IRF3. Enzyme‐linked immunoassay (ELISA) was performed to detect the cytokines including IFN‐β, TNF, or IL‐6 downstream of cGAS‐STING.ResultsMiR‐4691‐3p expression was increased in human dental pulp tissue with irreversible pulpitis. Treatment of HDPCs using recombinant human IFN‐β, TNF, or IL‐6 also upregulated miR‐4691‐3p. The bioinformatic prediction and luciferase reporter assay confirmed that STING was a direct target of miR‐4691‐3p. The miR‐4691‐3p mimic suppressedSTING expression, the phosphorylation of TBK1, p65, and IRF3, and the IFN‐β, TNF, or IL‐6 production. In contrast, the miR‐4691‐3p inhibitor enhanced the STING expression, the phosphorylation of TBK1, p65, and IRF3, and the IFN‐β, TNF, or IL‐6 production.ConclusionsMiR‐4691‐3p negatively regulates the cGAS‐STING pathway by directly targeting STING. This provides insight to utilize miRNA‐dependent regulatory effect to treat endodontic disease as well as STING‐dependent systemic inflammatory disease.

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Expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 6 in human dental pulp tissues and cells

Cited by 4 publications

References 32 publications

Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis—A Systematic Review

Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis—A Systematic Review

NLRP6‐caspase 4 inflammasome activation in response to cariogenic bacterial lipoteichoic acid in human dental pulp inflammation

MicroRNA‐4691‐3p inhibits the inflammatory response by targeting STING in human dental pulp cells: A laboratory investigation

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