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.
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Toll样受体4通过抑制Bmi-1表达激活NLRP3炎症小体途径和牙周炎症
DOI：
10.3892/ijmm.2020.4787
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发表时间：
2021-01
影响因子：
5.4
通讯作者：
Meng HY
中科院分区：
文献类型：
--
作者：
Qin ZY;Gu X;Chen YL;Liu JB;Hou CX;Lin SY;Hao NN;Liang Y;Chen W;Meng HY
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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DOI：
10.3402/pba.v2i0.18052
发表时间：
2012
期刊：
Pathobiology of aging & age related diseases
影响因子：
--
作者：
Asquith M;Haberthur K;Brown M;Engelmann F;Murphy A;Al-Mahdi Z;Messaoudi I
通讯作者：
Messaoudi I
影响因子：
6.7
作者：
Kinney JS;Morelli T;Oh M;Braun TM;Ramseier CA;Sugai JV;Giannobile WV
通讯作者：
Giannobile WV
二甲双胍预防氧化应激诱导的人牙周膜细胞衰老
影响因子：
4.5
作者：
Kuang, Yunchun;Hu, Bo;Song, Jinlin
通讯作者：
Song, Jinlin
影响因子：
4.2
作者：
Kim KA;Jeong JJ;Yoo SY;Kim DH
通讯作者：
Kim DH
影响因子：
3.9
作者：
Fathi, Ezzatollah;Farahzadi, Raheleh
通讯作者：
Farahzadi, Raheleh