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Association of high 5-hydroxymethylcytosine levels with Ten Eleven Translocation 2 overexpression and inflammation in Sjögren's syndrome patients
Clinical Immunology ( IF 8.6 ) Pub Date : 2018-06-09 , DOI: 10.1016/j.clim.2018.06.002
Carolina Lagos 1 , Patricia Carvajal 1 , Isabel Castro 2 , Daniela Jara 1 , Sergio González 3 , Sergio Aguilera 4 , María-José Barrera 1 , Andrew F G Quest 1 , Verónica Bahamondes 2 , Claudio Molina 5 , Ulises Urzúa 6 , Marcela A Hermoso 7 , Cecilia Leyton 2 , María-Julieta González 1
Affiliation  

Here, we determined the 5-hydroxymethylcytosine (5hmC), 5-methylcytosine (5mC), Ten Eleven Translocation (TETs), and DNA methyltransferases (DNMTs) levels in epithelial and inflammatory cells of labial salivary glands (LSG) from Sjögren's syndrome (SS)-patients and the effect of cytokines on HSG cells. LSG from SS-patients, controls and HSG cells incubated with cytokines were analysed. Levels of 5mC, 5hmC, DNMTs, TET2 and MeCP2 were assessed by immunofluorescence. In epithelial cells from SS-patients, an increase in TET2, 5hmC and a decrease in 5mC and MeCP2 were observed, additionally, high levels of 5mC and DNMTs and low levels of 5hmC were detected in inflammatory cells. Cytokines increased TET2 and 5hmC and decreased 5mC levels. Considering that the TET2 gene.promoter contains response elements for transcription factors activated by cytokines, together to in vitro results suggest that changes in DNA hydroxymethylation, resulting from altered levels of TET2 are likely to be relevant in the Sjögren's syndrome etiopathogenesis.



中文翻译:

干燥综合征患者中高 5-羟甲基胞嘧啶水平与 10-11 易位 2 过表达和炎症的相关性

在这里,我们确定了干燥综合征 ( SS ) 唇唾液腺 (LSG) 上皮细胞和炎症细胞中 5-羟甲基胞嘧啶 (5hmC)、5-甲基胞嘧啶 (5mC)、十一个十一易位 (TET) 和 DNA 甲基转移酶 (DNMT) 的水平)-患者和细胞因子对 HSG 细胞的影响。分析了来自 SS 患者、对照和与细胞因子一起孵育的 HSG 细胞的 LSG。通过免疫荧光评估 5mC、5hmC、DNMT、TET2 和 MeCP2 的水平。在来自 SS 患者的上皮细胞中,观察到 TET2、5hmC 增加以及 5mC 和 MeCP2 减少,此外,在炎症细胞中检测到高水平的 5mC 和 DNMT 以及低水平的 5hmC。细胞因子增加 TET2 和 5hmC 并降低 5mC 水平。考虑到 TET2 基因启动子包含由细胞因子激活的转录因子的反应元件,体外结果表明,由 TET2 水平改变引起的 DNA 羟甲基化变化可能与干燥综合征的发病机制有关。

更新日期:2018-06-09
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