possible therapeutic application of gene therapy of anti-inflammatory cytokines to rheumatoid joint destruction
| Project/Area Number |
17591557
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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 |
Orthopaedic surgery
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| Research Institution | University of Toyama |
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Principal Investigator |
SUGIYAMA Eiji University of Toyama, Interna Medicine 1, Associate professor (70179167)
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| Co-Investigator(Kenkyū-buntansha) |
岸 裕幸 富山大学, 准教授 (60186210)
MURAGUCHI Atsushi (MURAGUCHI Akira) University of Toyama, Professor (20174287)
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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 |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Rheumatoid arthritis / osteoclast / c-Fos / adeno-associated virus / interleukin-4 / Interleukin-10 / PPARγ agonists / TNFα / インターロイキン4 / 遺伝子療法 |
|---|
| Research Abstract |
Rheumatoid Arthritis (RA) is characterized by destruction of joint cartilage and bone, and osteoclasts are the principal cell type responsible for bone resorption in RA. Therefore, osteoclasts are real targets for the treatment of RA. In this study, we found that IL-4 and IL-10, anti-inflammatory cytokines, inhibited osteoclast differentiation via suppression of c-Fos in murine bone marrow cells. In addition, we showed that adeno-associated virus vector of IL-4 (AAV-IL-4) efficiently infected monocytes, precursor of osteoclasts, and that AAV-IL-4 inhibited TNFα-mediated osteoclastogenesis from human peripheral monocytes, suggesting that AAV-IL-4 gene therapy may be a promising therapeutic applicant for RA. Furthermore, we demonstrated that agonists of peroxisome proliferator-activated receptor γ (PPARγ), a new class of anti-inflammatory compounds, inhibited TNFα-mediated osteoclasts generation in human monocytes, and the inhibitory effect may be mediated in part by suppression of monocyte chemoattractant-1 (MCP-1). In summary, we proposed two types of therapeutic strategy, AAV-IL-4 gene therapy and PPARγ agonist, for rheumatoid joint destruction. We hope this project may contribute to the development of anti-rheumatic drugs.
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Report
(3 results)
Research Products
(21 results)
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[Journal Article] Isoproterenol suppresses cytokine-induced RANTES secretion in human lung epithelial cells through the inhibition of c-jun N-terminal kinase pathway2006
Author(s)
Miyabayashi K, Maruyama M, Yamada T, Shinoda C, Hounoki H, Kanatani Y, Shinoda K, Kawagishi Y, Miwa T, Suzuki K, Arai N, Hayashi R, Matsui S, Sugiyama E, Kobayashi M.
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Journal Title
Biochem Biophys Res Commun 350(3)
Pages: 753-61
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Ionizing radiation suppresses FAP-i mRNA level in A549 cells via p53 activation.2006
Author(s)
Yamada T, Maruyama M, Fujita T, Miyabayashi K, Shinoda C, KawagishiY, Fujishita T, Hayashi R, Miwa T, Arai N, Matsui S, Sugiyama E, Kobayashi M.
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Journal Title
FEBS Lett 580(18)
Pages: 4387-91
Description
「研究成果報告書概要(欧文)」より
Related Report
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