DNA methylcytosine dioxygenase ten-eleven translocation 2 enhances lipopolysaccharide-induced cytokine expression in human dental pulp cells by regulating MyD88 hydroxymethylation
DNA methylcytosine dioxygenase ten-eleven translocation 2 enhances lipopolysaccharide-induced cytokine expression in human dental pulp cells by regulating MyD88 hydroxymethylation
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DNA甲基胞嘧啶双加氧酶11-1易位2通过调节MyD88羟甲基化增强脂多糖诱导的人牙髓细胞细胞因子表达
DOI：
10.1007/s00441-018-2826-x
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发表时间：
2018-04
影响因子：
3.6
通讯作者：
Xu Qiong
中科院分区：
文献类型：
--
作者：
Wang Xinxuan;Feng Zhihui;Li Qimeng;Yi Baicheng;Xu Qiong
牙髓炎症是一种细菌驱动的炎症过程，其特征是参与牙髓破坏性过程的细胞因子/趋化因子在局部积聚。牙髓炎症涉及多种机制，包括表观遗传事件，如DNA甲基化/去甲基化。TET2是新近发现的一种DNA甲基胞嘧啶双加氧酶，在炎症性疾病中发挥重要作用。然而，它在牙髓炎症反应中的作用尚不清楚。我们观察到脂多糖(LPS)刺激人牙髓细胞(HDPC)后，TET2的mRNA和蛋白水平升高。为确定TET2对细胞因子表达的影响，将TET2基因敲除，并用细胞因子抗体阵列检测细胞因子在内毒素刺激后的表达。TET2基因敲除后，内毒素诱导的hDPC中GM-CSF、IL-6、IL-8和RANTES的蛋白表达减少。实时定量聚合酶链式反应和酶联免疫吸附试验进一步证实IL-6和IL-8的表达下调。此外，Ikk-α/β、p65和I-κBα信号通路的磷酸化水平在TET2沉默组降低。此外，在TET2缺陷的hDPC中，全局5-羟甲基胞嘧啶(5hmC)水平显著降低，基因组5-甲基胞嘧啶(5mC)水平显著升高，TET2缺失导致MyD88启动子在脂多糖刺激后5hmC水平降低。这些结果表明，TET2基因敲除通过下调MyD88羟甲基化来抑制内毒素诱导的hDPC的炎症反应。因此，TET2依赖的DNA去甲基化可能作为表观遗传调节因子在牙髓炎症中发挥重要作用。
Dental pulp inflammation is a bacterially driven inflammation process characterized by the local accumulation of cytokines/chemokines that participate in destructive processes in the pulp. Multiple mechanisms are involved in dental pulp inflammation, including epigenetic events, such as DNA methylation/demethylation. Ten-eleven translocation 2 (TET2) is a recently discovered DNA methylcytosine dioxygenase that plays important roles in inflammatory disease. However, its role in the inflammatory response of dental pulp is unknown. We observed elevated mRNA and protein levels of TET2 after lipopolysaccharide (LPS) stimulation in human dental pulp cells (hDPCs). To identify the effects of TET2 on cytokine expression, TET2 was knocked down and cytokines were detected using a cytokine antibody array after LPS stimulation. The protein expression of GM-CSF, IL-6, IL-8 and RANTES decreased in the LPS-induced hDPCs following TET2 knockdown. The downregulated expression levels of IL-6 and IL-8 were further confirmed by real-time quantitative polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Additionally, the phosphorylation levels of IKK-α/β, p65 and IκBα of the NF-κB signaling pathway were decreased in the TET2-silenced group. Furthermore, the global 5-hydroxymethylcytosine (5hmC) level was significantly decreased and the genomic 5-methylcytosine (5mC) level was increased in the TET2-deficient hDPCs; TET2 depletion resulted in a decrease in the 5hmC level of the MyD88 promoter following LPS stimulation. These findings indicate that TET2 knockdown inhibits LPS-induced inflammatory response in hDPCs by downregulating MyD88 hydroxymethylation. Thus, TET2-dependent DNA demethylation might play an important role in dental pulp inflammation as an epigenetic regulator.
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DOI：
10.1590/s1678-77572009000500031
发表时间：
2009-09
期刊：
Journal of applied oral science : revista FOB
影响因子：
--
作者：
Silva AC;Faria MR;Fontes A;Campos MS;Cavalcanti BN
通讯作者：
Cavalcanti BN
影响因子：
8.5
作者：
Y. Wu;H. Sun;F. Song;D. Fu;J. Wang
通讯作者：
Y. Wu;H. Sun;F. Song;D. Fu;J. Wang
影响因子：
--
作者：
Kim TW;Lee SJ;Oh BM;Lee H;Uhm TG;Min JK;Park YJ;Yoon SR;Kim BY;Kim JW;Choe YK;Lee HG
通讯作者：
Lee HG
DOI：
10.1056/nejmoa1701719
发表时间：
2017-07-13
期刊：
The New England journal of medicine
影响因子：
--
作者：
Jaiswal S;Natarajan P;Silver AJ;Gibson CJ;Bick AG;Shvartz E;McConkey M;Gupta N;Gabriel S;Ardissino D;Baber U;Mehran R;Fuster V;Danesh J;Frossard P;Saleheen D;Melander O;Sukhova GK;Neuberg D;Libby P;Kathiresan S;Ebert BL
通讯作者：
Ebert BL
DOI：
10.1126/science.1170116
发表时间：
2009-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tahiliani M;Koh KP;Shen Y;Pastor WA;Bandukwala H;Brudno Y;Agarwal S;Iyer LM;Liu DR;Aravind L;Rao A
通讯作者：
Rao A