2005 Fiscal Year Final Research Report Summary
DNA microarray-based approach for identifying new therapeutic targets in neuroimmunological diseases
| Project/Area Number |
16390258
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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 |
Neurology
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| Research Institution | National Center of Neurology and Psychiatry (N.C.N.P.) |
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Principal Investigator |
YAMAMURA Takashi N.C.N.P, Dept. of Immunology, Head, 疫病研究第六部, 部長 (90231670)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Jun-ichi N.C.N.P, Dept. of Immunology, Section Chief, 免疫研究部, 室長 (30274591)
MIYAKE Sachiko N.C.N.P, Dept. of Immunology, Section Chief, 免疫研究部, 室長 (50266045)
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| Project Period (FY) |
2004 – 2005
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| Keywords | multiple sclerosis / T cells / DNA microarray / NR4A2 / inflammation / interferon / chemokine / apoptosis |
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| Research Abstract |
Using a custom cDNA microarray, we have analyzed gene expression profiling of peripheral blood T cells derived from multiple sclerosis (MS) who are untreated or treated with interferon (IFN)-β. This study was aimed at obtaining insights into the pathogenesis of MS and the mechanism of action of IFN-β. We have found that a number of genes up- or down-regulated in MS T cells, are those related to apoptosis, inflammation, or DNA damage-regulation. Among apoptosis-related genes up-regulated in MS, we have chosen Nurr4A2 (Nurrl) and analyzed the implication in depth. NR4A2 is known to target osteopontin (OPN), a Th1 cytokine, thought to be involved in the pathogenesis of MS. We hypothesized that NR4A2 and OPN might be coordinately altered in MS, but this was not the case. Rather, we found that expression of NR4A2 would strongly correlate with that of IkB alpha and IkB ipsilon, targeted by NFkB or that of TNFAIP3, that is inducible with TNF signaling. This suggests that NFkB linked signals would cause the change of gene expression, which is probably corrected by anti-inflamunatory therapy. We also investigated IFN-responsive genes in human MS by analyzing the blood from IFN-treated patients. Immediately induced genes contained inflammatory cytokines such as IL-6 and inflammatory chemokines such as CXCR3 ligand, which would account for the early side effects of IFN-b in MS patients, including headache and fever up. These results may suggest the importance of anti-inflammatory therapy in MS.
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[Journal Article] T cell gene expression profiling identifies distinct subgroups of Japanese multiple sclerosis patients2006
Author(s)
Jun-ichi Satoh, Megumi Nakanishi, Fumiko Koike, Hiroyuki Onoue, Toshimasa Aranami, Toshiyuki Yamamoto, Mitsuru Kawai, Seiji Kikuchi, Kyouichi, Nomura Kazumasa Yokoyama, Kohei Ota, Toshiro Saito, Masayuki Ohta, Sachiko Miyake, Takashi Kanda, Toshiyuki Fukazawa, Takashi Yamamura
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Journal Title
Journal of Neuroimmunology Vol.174
Pages: 108-118
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis2005
Author(s)
Jun-ichi Satoh, Megunii Nakanishi, Fumiko Koike, Sachiko Mime, Toshiyuki Yamamoto, Mitsuru Kawai, Seiji Kikuchi, Kyouichi Nomura, Kazumasa Yokoyama, Kohei Ota, Takashi Kanda, Toshiyuki Fukazawa, Takashi Yamamura.
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Journal Title
Neurobiology of Disease Vol.18, No.3
Pages: 537-550
Description
「研究成果報告書概要(欧文)」より
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