Development of the novel therapeutic method for rheumatoid arthritis based on the redox regulation
| Project/Area Number |
15591054
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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 | Kobe University |
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Principal Investigator |
KOSHIBA Masahiro Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70301827)
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| Co-Investigator(Kenkyū-buntansha) |
KUMAGAI Shunichi Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00153346)
NAKAMURA Hajime Kyoto University, Hospital, Associate Professor, 医学部・検索医療センター, 助教授 (70303914)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | rheumatoid arthritis / oxidative stress / thioredoxin / animal model / experimental arthritis model / adenosine / synoviocytes / therapy / 遺伝子導入マウス |
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| Research Abstract |
1.Anti-arthritis effects of thioredoxin (TRX) transgenic mice (TRX-Tg)
Since TRX-Tg have C57BL/6 background and are resistant to collagen-induced arthritis, arthritis was induced by the intraperitoneal injection of anti-collagen type II monoclonal antibody cocktail.
(1)Arthritis was 100% induced at day 6 on wild-type mice (Wt) while only few TRX-Tg developed arthritis on day 7, thus the late onset of arthritis was observed.
(2)On Wt, joint redness and swelling were significant and the joint scores were 7 to 14 (average 10). On TRX-Tg only slight, if any, joint redness and swelling were observed and the joint scores were 0 (no arthritis) to 2.
(3)Histologically synovial proliferation, neutrophil infiltration and cartilage destruction were mild in TRX-Tg compared to Wt. Inhibition of cartilage apoptosis was proved.
2.Anti-arthritis effects of exogenous TRX
Arthritis was induced in the same manner on Wt and recombinant TRX (rTRX) was injected intraperitoneally every day. Onset of arthritis was similarly delayed one day by rTRX administration. Inhibition of joint swelling was also achieved by rTRX administration but not as strong as was observed on TRX-Tg.
These results indicate that the inhibition of oxidative stress by enough amount of TRX may lead to the novel therapeutic method for rheumatoid arthritis (RA).
3.The effect of adenosine on TRX expression of synoviocytes
To investigate if the anti-oxidative function of adenosine, the effector molecule of anti-rheumatic effects of methotrexate, is related to the TRX, synoviocytes from RA patients were incubated with adenosine and the change of TRX expression was estimated by ELISA and flow cytometry. Adenosine had no influence to the TRX levels, which suggests that anti-rheumatic effects of adenosine may not be at least directly related to the TRX.
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Report
(3 results)
Research Products
(12 results)
