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KMID : 0388220070140010023
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Journal of the Korean Rheumatism Association
2007 Volume.14 No. 1 p.23 ~ p.30
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The Effect of Estrogen on the DNA Methylation of B Cells in Patients with SLE
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Park Mi-Kyung
Park Sung-Hwan
Kwok Seung-Ki
Cho Mi-La
Kim Ho-Youn
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Abstract
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Objective: Epigenetics is an important, alternative mechanism of gene regulation that is independent of the nucleotide sequences of DNA. We investigated mRNA levels for DNA methyltransferase-1 (DNMT-1), and the effect of estrogen on the expression of DNMT-1 level in T cells and B cells from patients with systemic lupus erythematosus (SLE) and healthy subjects, and assessed the possible etiological role of DNA methylation in the pathogenesis of SLE.
Methods: mRNA levels for DNMT-1 in CD4? T cells and CD19? B cells from 37 patients with SLE and 12 healthy controls were examined using RT-PCR. We used specific primer for DNMT-1 and β actin, The effect of estrogen on the DNA methylation was measured by the mRNA level of DNMT-1 CD4? T cells and CD19? B cells treated with 100 nM of 17β-estradiol for 72 hour.
Results: The levels of DNMT-1 mRNA were significantly lower in CD4? T cells and CD19? B cells from SLE patients compared with healthy controls. We observed the suppression of the levels of DNMT-1 mRNA by stimulated with estrogen in patients with SLE patients, especially in CD19?B cells. DNA hypomethylation of B cells was tend to be correlated with the level of anti-ds DNA antibody without statistical significance (r=?0.43, p=0.3).
Conclusion: Our observations suggest that suppression of DNMT-1 by estrogen in B cells from patients with SLE might be related to the pathogenesis of SLE. Epigenetic studies may provide clues for developing new treatment strategies of SLE.
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KEYWORD
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Systemic lupus erythematosus, DNA methyltransferase-1, DNA methylation, Estrogen
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