| Project/Area Number |
20591173
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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 | Nagasaki University |
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Principal Investigator |
KAWAKAMI Atsushi Nagasaki University, 医歯薬学総合研究科, 教授 (90325639)
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| Co-Investigator(Kenkyū-buntansha) |
ABIRU Norio 長崎大学, 病院, 講師 (00380981)
TAMAI Mami 長崎大学, 保健・医療推進センター, 助教 (60380862)
IDA Hiroaki 長崎大学, 病院, 講師 (60363496)
FUJIKAWA Keita 長崎大学, 病院, 医員 (90404285)
KAWASHIRI Shinya 長崎大学, 病院, 医員 (20457576)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 関節リウマチ / 滑膜細胞 / 免疫担当細胞 / CaMKII / シトルリン化 / PADIs / CaMK II / 滑膜線維芽細胞 / 抗CCP抗体 / 骨髄浮腫 / 滑膜線維芽細胞(FLS) / PADI2 / PADI4 / 蛋白シトルリン化 / Treg / HL-60 / 末梢血単核球(PBMC) / ヒストン |
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| Research Abstract |
We have examined the relationship between the pathogenesis of rheumatoid arthritis (RA) and CaMKII/PADIs/peptide citrullination/cellular abnormality of synovial cells and immune competent cells. Expression of PADIs in the rheumatoid synovial tissues remains to be clarified at present. According to our data, the expression of PADIs was weak whereas that of PADIs substrates were present in rheumatoid synovial cells. PADIs substrates in rheumatoid synovial cells could be citrullinated by interaction with neighboring immune competent cells, resulting in stimulation of anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) in patients with RA. Our present data also suggested that the function of regulatory T cells (Treg cells), a major immune competent cell population, is down-regulated in patients with RA that may associate with perpetuation of the disease's process. However, further investigation is necessary to identify whether these phenomena are primary events or secondary results. In addition, the investigations regarding to the association of Treg cells with CaMKII/PADIs are also be necessary. In clinical study, we have identified a close association of MRI-proven bone edema with anti-CCP antibodies. At present, a detection of peptide citrullination is very difficult. Therefore, we are also going to solve this problem by immune complexsome analysis.
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