| Project/Area Number |
17390290
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | Osaka University |
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Principal Investigator |
NISHIMOTO Norihiro Graduate School Of Frontier Biosciences, Laboratory Of Immune Regulation, Professor, 生命機能研究科, 教授 (80273663)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOTA Syunnpei Yokohama City University School of Medicine, Professor, 医学研究院, 教授 (10158363)
MIMA Touru Graduate School Of Frontier Biosciences, Laboratory Of Immune Regulation, associate professor, 生命機能研究科, 助教授 (30373517)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2006: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 2005: ¥10,300,000 (Direct Cost: ¥10,300,000)
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| Keywords | signal transduction / DNA microarray / immunology / drug efficacy / DNAマイクロアレイ / IL-6阻害治療 / インターフェロンα / defellsin-α / インターフェロン / defensin-α |
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| Research Abstract |
We have confirmed the efficacy of an anti-Interleukin-6 (IL-6) receptor antibody, tocilizumab, for rheumatoid arthritis (RA) and systemic-onset juvenile idiopathic arthritis (soJIA). IL-6 blockade increased serum androgen which has anti-inflammatory effect for RA. IL-6 blockade also retarded the progression of joint damage and the long-term efficacy was predicted by the decrease in the serum MMP-3, CRP and PIIANP in the first 3 months after the start of tocilizumab. In the patients with soJIA, an exhaustive DNA microarray analysis of mRNA expression revealed 24 molecules differentially expressed compared to healthy donors. Those included the molecules related to innate immunity, signal transduction and cell growth. Gene Ontology and Network, Pathway analysis also revealed the stimulation of IFN-γ, TNF cascades in both soJIA and polyarticular JIA. ATP synthesis related genes were down-regulated only in soJIA. These molecules might play a pathological role in soJIA. We are now studying a pathological role in relation to IL-6. In systemic lupus erythematosus (SLE), DNA microarray analysis identified 24 molecules which include 9 IFN-α-inducible genes and defensin-α3. We have also established new receptor inhibitor of IL-6 (NRI) which is feasible to gene therapy.
We have identified several candidate molecules which play pathological roles in these autoimmune diseases. The in vivo functions of them are being studied.
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