| Project/Area Number |
10470126
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Osaka University |
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Principal Investigator |
NISHIMOTO Norihiro School of Health and Sport Sciences, Osaka University Associate Professor, 健康体育部, 助教授 (80273663)
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| Co-Investigator(Kenkyū-buntansha) |
OCHI Takahiro Graduate School of Medicine, Osaka University, Professor, 医学系研究科, 教授 (80112035)
YOSHIZAKI Kazuyuki School of Health and Sport Sciences, Osaka University, Professor, 健康体育部, 教授 (90144485)
MATSUMOTO Tomoshige School of Health and Sport Sciences, Osaka University, Assistant Professor, 健康体育部, 助手 (10311763)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Rheumatoid Arthritis / Cytokine / Interleukin 6 (IL-6) / TNFα / Humanized Antibody / IL-6 receptor / SSI-1 / Negative feedback / インターロイキン6 / 滑膜細胞 |
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| Research Abstract |
1. Inhibitory effects of anti-interleukin-6 receptor antibody (anti-IL-6R Ab) against murine and similar collagen-induced arthritis and joint destruction were elucidated.
2. Humanized anti-IL-6R Ab was proven to be effective to patients with refractory rheumatoid arthritis (RA) and thus confirming that IL-6 plays a major role in the RA pathology. It also shows IL-6 signal blocking can be a new therapy for RA.
3. IL-6 in the presence of soluble IL-6R (sIL-6R) inhibits the growth of synovial cells. TNFα-induced IL-6 can be a negative feedback factor of TNFα-induced synovial cell proliferation in RA.
4. Therapeutic effects of IL-6 blockade were through elimination of inflammatory cell penetrating the RA synovial tissue and also through inhibition of angiogenesis and osteoclast formation.
5. STATs-induced STATs inhibitor-1 and its family molecule SSI-3 as negative feed back factors of intracytoplasmic IL-6 signaling may be involved in the chronic inflammatory status of RA.
6. These results indicate the possibility of new therapeutic approach for RA by blocking IL-6 signaling based on the pathophysiology of RA.
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