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

  • Authors:
    • Zi‑Yue Qin
    • Xin Gu
    • Yu‑Lian Chen
    • Jia‑Bao Liu
    • Chen‑Xing Hou
    • Shi‑Yu Lin
    • Nan‑Nan Hao
    • Yan Liang
    • Wu Chen
    • Hao‑Yu Meng
  • View Affiliations / Copyright

    Affiliations: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Clinical Research, Friendship Plastic Surgery Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
    Copyright: © Qin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 137-150
    |
    Published online on: November 11, 2020
       https://doi.org/10.3892/ijmm.2020.4787
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Abstract

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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Copy and paste a formatted citation
Spandidos Publications style
Qin ZY, Gu X, Chen YL, Liu JB, Hou CX, Lin SY, Hao NN, Liang Y, Chen W, Meng HY, Meng HY, et al: Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression. Int J Mol Med 47: 137-150, 2021.
APA
Qin, Z., Gu, X., Chen, Y., Liu, J., Hou, C., Lin, S. ... Meng, H. (2021). Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression. International Journal of Molecular Medicine, 47, 137-150. https://doi.org/10.3892/ijmm.2020.4787
MLA
Qin, Z., Gu, X., Chen, Y., Liu, J., Hou, C., Lin, S., Hao, N., Liang, Y., Chen, W., Meng, H."Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression". International Journal of Molecular Medicine 47.1 (2021): 137-150.
Chicago
Qin, Z., Gu, X., Chen, Y., Liu, J., Hou, C., Lin, S., Hao, N., Liang, Y., Chen, W., Meng, H."Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression". International Journal of Molecular Medicine 47, no. 1 (2021): 137-150. https://doi.org/10.3892/ijmm.2020.4787
Copy and paste a formatted citation
x
Spandidos Publications style
Qin ZY, Gu X, Chen YL, Liu JB, Hou CX, Lin SY, Hao NN, Liang Y, Chen W, Meng HY, Meng HY, et al: Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression. Int J Mol Med 47: 137-150, 2021.
APA
Qin, Z., Gu, X., Chen, Y., Liu, J., Hou, C., Lin, S. ... Meng, H. (2021). Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression. International Journal of Molecular Medicine, 47, 137-150. https://doi.org/10.3892/ijmm.2020.4787
MLA
Qin, Z., Gu, X., Chen, Y., Liu, J., Hou, C., Lin, S., Hao, N., Liang, Y., Chen, W., Meng, H."Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression". International Journal of Molecular Medicine 47.1 (2021): 137-150.
Chicago
Qin, Z., Gu, X., Chen, Y., Liu, J., Hou, C., Lin, S., Hao, N., Liang, Y., Chen, W., Meng, H."Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression". International Journal of Molecular Medicine 47, no. 1 (2021): 137-150. https://doi.org/10.3892/ijmm.2020.4787
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