Hypomethylation of interleukin-4 and -6 promoters in T cells from systemic lupus erythematosus patients.
Acta Pharmacol Sin
; 29(1): 105-12, 2008 Jan.
Article
em En
| MEDLINE
| ID: mdl-18158872
ABSTRACT
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 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 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Interleucina-4
/
Interleucina-6
/
Lúpus Eritematoso Sistêmico
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Acta Pharmacol Sin
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
China