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

• Published in: Acta pharmacologica Sinica Vol. 29; no. 1; pp. 105 - 112
• Main Authors: Mi, Xiang-bin, Zeng, Fan-qin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2008; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Adult; Antimetabolites, Antineoplastic - pharmacology; Azacitidine - pharmacology; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; DNA - biosynthesis; DNA - genetics; Female; Humans; Immunology; Interleukin-4 - genetics; Interleukin-6 - genetics; interleukin‐4; interleukin‐6; Internal Medicine; Lupus Erythematosus, Systemic - metabolism; Male; Medical Microbiology; Methylation; original-article; Pharmacology/Toxicology; promoter; Reverse Transcriptase Polymerase Chain Reaction; systemic lupus erythematosus; T-Lymphocytes - metabolism; T细胞; Vaccine; 甲基化; 白细胞素; 系统性红斑狼疮; interleukin-4; systemic lupus erythematosus; promoter; methylation; interleukin-6
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1111/j.1745-7254.2008.00739.x

Aim： DNA methylation regulates gene expression, and hypomethylation is associated with abnormal T-cell function in systemic lupus erythematosus （SLE）. However, little is known about the methylation levels of the intedeukin （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 demethylated the CpG islands in the 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 patients 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.