A Sialidase‐Deficient <i>Porphyromonas gingivalis</i> Mutant Strain Induces Less Interleukin‐1β and Tumor Necrosis Factor‐α in Epi4 Cells Than W83 Strain Through Regulation of c‐Jun N‐Terminal Kinase Pathway

Li, Chen; Yang, Xue; Pan, Yaping; Yu, Na; Xu, Xiaoyu; Tong, Tong; Tang, Xiaolin; Zhang, Dongmei; Liu, Jingbo; Li, Lin

doi:10.1902/jop.2017.160815

Cited by 9 publications

(12 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are two possible reasons for this observation. The first reason might be that the lack of sialidase reduces the activity of important P. gingivalis virulence factors, such as fimbriae, LPS, capsule, and gingipains (Aruni et al, 2011 ; Li et al, 2012 , 2017 ). Virulence factors of P. gingivalis affect the interaction with macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…The construction of ΔPG0352 and comΔPG0352 were as previously described (Li et al, 2017 ). Porphyromonas gingivalis W83, ΔPG0352 and comΔPG0352 were cultured on tryptic soy blood (TSB) agar plates supplemented with 5% sheep blood, 5% yeast extract, hemin (5 μg/ml) and 0.1% vitamin K under anaerobic conditions at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…Sialidase deficiency did not influence P. gingivalis growth, but showed less pathogenicity than the wild-type strain in a mouse abscess model (Li et al, 2012 ), while the mechanism remains unknown. Our previous study and the study of Aruni W et al showed that the existence of sialidase was associated with the expression of virulence factors in P. gingivalis , including fimbriae, gingipain, capsule, and LPS (Aruni et al, 2011 ; Li et al, 2017 ). The sialylation on the surface of pathogen made it difficult to be recognized by macrophages, allowing escape from the hosts' defense.…”

Section: Introductionmentioning

confidence: 96%

See 2 more Smart Citations

Sialidase Deficiency in Porphyromonas gingivalis Increases IL-12 Secretion in Stimulated Macrophages Through Regulation of CR3, IncRNA GAS5 and miR-21

Yang

Pan

et al. 2018

Front. Cell. Infect. Microbiol.

Self Cite

View full text Add to dashboard Cite

Porphyromonas gingivalis (P. gingivalis) is a major periodontal pathogen that can induce an immune response leading to a destructive inflammatory process. During the inflammatory process, interleukin-12 (IL-12) is secreted, correlating with bacterial clearance by macrophages. Bacterial sialidase has recently been shown to influence the synthesis and modification of the macromolecules on its surface, and is associated with the interaction between bacteria and host cells. We have previously constructed a P. gingivalis sialidase gene mutant strain in P. gingivalis W83 (ΔPG0352) and found that ΔPG0352 showed less pathogenicity than the wild-type strain. In this study, U937-differentiated macrophages were stimulated by P. gingivalis W83, ΔPG0352, or PG0352 complemented strain (comΔPG0352). Transmission electron microscopy showed that P. gingivalis caused a loss of membrane integrity in macrophages and the intracellular bacteria were enclosed within endocytic vacuoles. The expression of both IL-12p35 and IL-12p40 genes and the levels of IL-12p70 were significantly higher in U937 stimulated by ΔPG0352 than in those with P. gingivalis W83 and comΔPG0352. In order to explain why ΔPG0352 induced more IL-12 in macrophages, immunofluorescence assays, PCR arrays, and gene silence or overexpression experiments were carried out. Immunofluorescence assays showed that ΔPG0352 induced lower expression of CR3 in macrophages. After CR3 was suppressed, there were no significant differences in the IL-12p70 levels between macrophages stimulated by P. gingivalis W83, ΔPG0352 or comΔPG0352. PCR array experiments showed that miR-21 and lncRNA GAS5 were differentially expressed between macrophages stimulated by P. gingivalis W83 and ΔPG0352, which had been identified by real-time PCR. The results of CR3 blocking and lncRNA GAS5 gene silence or overexpression showed that the difference in IL-12 levels between P. gingivalis W83 and ΔPG0352 groups was associated with CR3, lncRNA GAS5 and miR-21. Thus it can be concluded that the sialidase-deficient strain is more easily cleared by attenuating CR3 activation, reducing the inhibition of lncRNA GAS5, inducing less miR-21 and more IL-12 in macrophages. These results indicate that inhibiting the activity of sialidase in P. gingivalis will cause rapid clearing by macrophages.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

Sialidase Deficiency in Porphyromonas gingivalis Increases IL-12 Secretion in Stimulated Macrophages Through Regulation of CR3, IncRNA GAS5 and miR-21

Yang

Pan

et al. 2018

Front. Cell. Infect. Microbiol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Expression levels of the genes, fimA , fimR , fimS , kgp , rgpA , and rgpB , in P. gingivalis were determined by real‐time PCR. P. gingivalis (10 7 CFU/mL) was treated with 1 mM DANA for 12 hours, then total RNA isolated, and quantitative real‐time PCR was performed as described previously 15 . Primer sequences are listed in Supplementary Table 1 in online Journal of Periodontology .…”

Section: Methodsmentioning

confidence: 99%

“…One particular enzyme that functions as a potential virulence factor is sialidase (neuraminidase) 13 . Our previous studies demonstrated that sialidase‐deficient mutants of P. gingivalis fail to produce an intact capsule, form less biofilm, have lower gingipain activity, cause rapid clearance by macrophages, and exhibit reduced virulence in a mouse abscess model 14‐17 . Therefore, suppression of sialidase using a sialidase inhibitor may be a potential method for alleviation of periodontitis.…”

Section: Introductionmentioning

confidence: 99%

The sialidase inhibitor, DANA, reduces Porphyromonas gingivalis pathogenicity and exerts anti‐inflammatory effects: An in vitro and in vivo experiment

Fan

Zheng

et al. 2020

Journal of Periodontology

Self Cite

View full text Add to dashboard Cite

Background Sialidase has an important role in the pathogenesis of periodontitis and Porphyromonas gingivalis is a sialidase‐producing organism implicated in periodontitis development. The aim of this study was to evaluate the anti‐virulence and anti‐inflammatory properties of the sialidase inhibitor, 2‐deoxy‐2,3‐didehydro‐N‐acetylneuraminic acid (DANA), in vitro and in vivo. Methods The effects of DANA on P. gingivalis sialidase and cell viability were determined, and the effects of DANA on P. gingivalis virulence were evaluated by assessment of growth curves, cell morphology, biofilm formation, fimbriae gene expression, and gingipains and lipopolysaccharide (LPS) activity. Anti‐inflammatory effects of DANA on LPS‐induced macrophages were assessed by measurement of tumor necrosis factor‐alpha (TNF‐α), interleukin (IL‐1β), inducible nitric oxide synthase (iNOS) secretions. The effect of DANA on P. gingivalis–induced periodontitis in rats was analyzed by radiography, stereoscopic microscopy, histopathology, and immunohistochemistry. Results Sialidase inhibition rate of 1mM DANA was 72.01%. Compared with untreated controls, treatment with DANA inhibited P. gingivalis growth and biofilm formation, and significantly decreased expression of the fimA, fimR, and fimS genes, as well as gingipains activity. DANA did not influence macrophage viability, but significantly inhibited TNF‐α, IL‐1β, and iNOS production in LPS‐stimulated macrophages. In the periodontitis rat model, DANA prevented alveolar bone absorption and inhibited TNF‐α and IL‐1β production. Conclusion DANA can reduce the growth, the biofilm formation and the virulence of P. gingivalis and exhibits anti‐inflammatory effects, as well as effects against rat periodontitis, suggesting that DANA should be considered for development as a new adjunctive treatment for periodontitis.

show abstract

SGK1 negatively regulates inflammatory immune responses and protects against alveolar bone loss through modulation of TRAF3 activity

Han

Ren

Lohner

et al. 2022

Journal of Biological Chemistry

View full text Add to dashboard Cite

A Sialidase‐Deficient Porphyromonas gingivalis Mutant Strain Induces Less Interleukin‐1β and Tumor Necrosis Factor‐α in Epi4 Cells Than W83 Strain Through Regulation of c‐Jun N‐Terminal Kinase Pathway

Abstract: A sialidase-deficient P. gingivalis mutant strain induces less IL-1β and TNF-α in epi4 cells than W83 strain through regulation of JNK pathway.

Cited by 9 publications

References 52 publications

Sialidase Deficiency in Porphyromonas gingivalis Increases IL-12 Secretion in Stimulated Macrophages Through Regulation of CR3, IncRNA GAS5 and miR-21

Sialidase Deficiency in Porphyromonas gingivalis Increases IL-12 Secretion in Stimulated Macrophages Through Regulation of CR3, IncRNA GAS5 and miR-21

The sialidase inhibitor, DANA, reduces Porphyromonas gingivalis pathogenicity and exerts anti‐inflammatory effects: An in vitro and in vivo experiment

SGK1 negatively regulates inflammatory immune responses and protects against alveolar bone loss through modulation of TRAF3 activity

Contact Info

Product

Resources

About