2004 Fiscal Year Final Research Report Summary
Elects of DNA methylation on the induction of systemic lupus erythematosus
| Project/Area Number |
15591064
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Juntendo University |
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Principal Investigator |
SEKIGAWA Iwao Juntendo University, School of Medicine, Associate professor, 医学部, 助教授 (80179332)
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| Co-Investigator(Kenkyū-buntansha) |
SEKIGAWA Iwao Juntendo University, School of Medicine, Associate Professor (80179332)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Ssystemic lupus erythematosus / Human endogenous retroviruses / DNA methylation / Autoimmunity / Drug-induced lupus / Demethylating agents |
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| Research Abstract |
We have reported the possible important role of human endogenous retroviruses (HERV) in the induction of systemic lupus erythematosus (SLE). Transcription and translation levels of BERV clone 4-1 are increased in the patients with SLE as compared to normal controls. In addition, peptides derived from HERV clone 4-1 can induce autoimmune phenomena including cytokine productions and polyclonal B cell activation in vitro. We also found that the transcriptionlevels of this HERV are regulated by DNA methyltransferase 1(DNMT1) activities, which is an enzyme of related to DNA methylation. Even in lymphocytes in normal volunteer, the demethylating agents such as 5-AZA C can induce the transcription of HERV with the decrease of DNMT1 levels. DNMT1 messenger RNA (mRNA) levels in SLE patients are lower as compared to normal control. Thus, the increase of HERV in SLE patients seems to be regulated by the decrease levels of DNMT1. It is interesting that many of drugs inducing SLE, such as hydralazine, methyldopa, and phenytoin, act as a demethylating agent. SLE is known to occur predominantly in female rather than male. Regarding this point, we have recently found that estrogen can reduce the transcription levels of DNMT1. This may be related to the gender bias of SLE. Our study indicated that transcriptuional increases of BERV as a internal auto-antigen is related to lower levels of DNMT1 in the patients with SLE and sex hormone such as estrogen reduce the levels of this DNMT1.
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