2003 Fiscal Year Final Research Report Summary
Identification of the transcriptional active region of the genome in autoimmune diseases.
| Project/Area Number |
14570407
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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 |
内科学一般
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SAWADA Tetsuji The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (50235470)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Tesufumi The University of-foreign Affairs, Health Care Center, Professor, 保健管理センター, 教授 (30092141)
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| Project Period (FY) |
2002 – 2003
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| Keywords | suppression PCR / DNA methylation / Nuclear factor kappaB |
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| Research Abstract |
Human endogenous retrovirus (HERV) sequences are dispersed throughout the genome, which are thus considered to be a useful genetic marker for genome research. HERVs may participate in the pathogenesis of autoimmunity, via the formation of immune complexes after translation, or activation of the surrounding genes via their promoter /enhancer activity. The demethylation of cytosine at the CpG islands is associated with transcriptional activity In this study, the profile of CAN methylation around the hhh s were examined by suppression ppp. Adapter primer was added to the genomic ddd, which was degested with methylation-sensitive restriction enzyme(HpaII). Suppression ppp was subsequently performed tor ampligy the HpaII fragments containing hhh sequences, using the primer for adapter sequence, and the fluorescence-labeled primer comon to the various hhh sss (U5 and U3 region ). S control, metylation-insensitve restriction enzyme(MspI) was used, and the length of fragments was analyzed by a
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utomatic sssr. The profile of suppression ppp using HpaII fragments as template was different between neutrophils and and lymph nodes. In contrast the profile using MspI fragments as template was identical. Therefore, it is considered that the different profile of suppression ppp may result from the methylation-status (epigenetic) defference among the tissues. As to rheumatoid arthritis (RA),PADI4 was demonstrated to be in RA, although the relevance of its methylation was unknown. On the other hand, NF-kB inhibitors was also investigated. Among the chemicals, designed via computere-assisted drug design, the compound was selected as most effective inhibitor of transcriptional NF-kB activity, the proliferation and the production of proinflammatory cytokines from synovial cell lines. The compund was effective in mouse collagen artrits model at a dosage of 1-3mg/kg, shich is promising as novel anti-rheumatic therapy, although further study investigating its safety profile is necessary. The effect of this compund on the methylation profile around perform for the analysis of the entire profile of methylation, it would be useful for the investigation of epigenetic factor (methylation status) of genome DNA in various autoimmune diseases. Less
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