Ultraviolet B enhances DNA hypomethylation of CD4+T cells in systemic lupus erythematosus via inhibiting DNMT1 catalytic activity
Ultraviolet B enhances DNA hypomethylation of CD4+T cells in systemic lupus erythematosus via inhibiting DNMT1 catalytic activity
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DOI：
10.1016/j.jdermsci.2013.04.022
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发表时间：
2013-09-01
影响因子：
4.6
通讯作者：
Shi, Weimin
中科院分区：
文献类型：
--
作者：
Wu, Zhouwei;Li, Xiaojie;Shi, Weimin
背景：CD4+T细胞DNA低甲基化参与了系统性红斑狼疮(SLE)的发病过程。最近的研究表明，紫外线B(UVB，290-320 nm)可能通过降低DNA甲基化水平而导致SLE的加重。然而，DNA甲基转移酶1(DNMT1)在中波紫外线(UVB)诱导的CD4+T细胞DNA低甲基化中的作用尚不清楚。目的：探讨DNMT1在UVB促进狼疮CD4+T细胞DNA整体甲基化中的作用。分析不同剂量UVB照射后SLE患者和健康对照组外周血中CD4+T细胞的变化。结果：SLE患者外周血中CD4+T细胞DNA甲基化水平和DNMT1基因表达水平均显著低于对照组。在UVB照射后，SLE患者的DNA甲基化水平以剂量依赖的方式减少，但在对照组中没有。UVB照射对SLE患者和健康对照组的DNMT1基因和蛋白表达水平均无影响。UVB照射后SLE患者CD4+T细胞DNMT1催化活性显著降低，且呈剂量依赖关系。活动期SLE患者CD4+T细胞DNMT1催化活性低于稳定期SLE患者，且对UVB暴露更敏感。结论：UVB通过剂量依赖性抑制SLE患者CD4+T细胞DNA低甲基化。(C)2013年日本皮肤病研究学会。爱思唯尔爱尔兰有限公司出版。版权所有。
Background: CD4+ T cells DNA hypomethylation is involved in the pathogenesis of systemic lupus erythematosus (SLE). Recent studies showed that ultraviolet B (UVB, 290-320 nm) might induce the exacerbation of SLE by decreasing the DNA methylation level. However, the role of DNA methyltransferase 1 (DNMT1) in the UVB-induced CD4+ T cells DNA hypomethylation remains unclear.Objective: To elucidate the role of DNMT1 in lupus CD4+ T cells global DNA hypomethylation enhanced by UVB.Methods: 35 SLE patients and 15 healthy controls were enrolled in the study. CD4+ T cells from SLE patients and healthy controls exposed to different dosages of UVB were analyzed. The global DNA methylation measurement, real-time PCR, Western blotting and DNMT1 catalytic activity detection were employed.Results: The level of global DNA methylation and DNMT1 mRNA expression in CD4+ T cells from SLE patients were significantly lower than those from the control group. DNA methylation was decreased after UVB exposure in a dosage-dependent manner in SLE patients, but not in the control group. DNMT1 mRNA and protein expression level were not affected by UVB exposure in both SLE patients and healthy controls. DNMT1 catalytic activity was significantly decreased in CD4+ T cells from SLE patients after UVB exposure in a dosage-dependent manner. DNMT1 catalytic activity was lower and more sensitive to UVB exposure in CD4+ T cells from active SLE patients that from stable ones.Conclusion: UVB enhanced DNA hypomethylation of CD4+ T cells in SLE via inhibiting DNMT1 catalytic activity in a dosage-dependent manner. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.