Hypomethylation of interleukin-4 and -6 promoters in T cells from systemic lupus erythematosus patients

• 来源期刊: 中国药理学报（英文版）
• 关键词: systemic lupus erythematosus methylation interleukin-4 interleukin-6 promoter
• 年，卷（期）: 2008,（1）
• 页码范围: 105-112
• 页数: 8页
• 语种: 英文
• DOI: 10.1111/j.1745-7254.2008.00739.x

摘要

Aim: DNA methylation regulates gene expression, and hypomethylation is asso-ciated with abnormal T-cell function in systemic lupus erythematosus (SLE). However, little is known about the methylation levels of the interleukin (IL)-4 and -6 promoters in SLE patients. Methods: T cells were isolated from 20 SLE patients and 10 healthy controls, activated in vitro in the presence or absence of 5-azacytidine (5-azaC), and their IL-4 and -6 transcripts were characterized using semiquantitative RT-PCR. Following bisulfate modification of their genomic DNA, the levels of DNA methylation in the IL-4 or -6 promoter were determined by nested PCR and direct sequencing. Results: The levels of IL-4 and -6 mRNA transcripts were significantly higher in SLE T cells, as compared with that in the controls. Furthermore, the treatment of healthy T cells with 5-azaC demethy lated the CpG islands IL-4 or -6 promoter and increased IL-4 and -6 mRNA transcriptions. Importantly, the hypomethylation of the CpG islands in the IL-4 and -6 promoters displayed in SLE paients was similar to that of healthy T cells treated with 5-azaC. Finally, the hypomethylation levels of the CpG islands in the IL-4 and -6 promoters in lupus patients were significantly correlated to the IL-4 and -6 expressions. Conclusion: The hypomethylation of the CpG islands of the IL-4 and -6 promoters accrued in T cells from SLE patients and was associated with the severity of SLE at the clinic.