| Project/Area Number |
11670436
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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 |
内科学一般
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| Research Institution | University of Tokyo |
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Principal Investigator |
HIRAI Koichi University of Tokyo, Graduate School of Medicine, Visiting Associate Professor, 大学院・医学系研究科, 客員助教授 (10156630)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Masao University of Tokyo, Graduate School of Medicine, Assistant Professor, 医学部・附属病院, 助手 (10302704)
中島 敏治 東京大学, 大学院・医学系研究科, 寄附講座教員 (20155724)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | eotaxin / eosinophil / bronchial asthma / allergy / inflammation / chemokine / CCR3 / interferon-γ / インターフェロンγ / Th1 / Th2 |
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| Research Abstract |
Eotaxin is a CC chemokine specifically binds to CC chemokine receptor (CCR)3, which is preferentially expressed on eosinophils. Eotaxin is implicated in pathogenesis of selective accumulation of eosinophils, which is a characteristic aspect of allergic inflammation. We established monoclonal antibodies against eotaxin and developed a high-sensitive ELISA system. Results of our research are follows.
1) Interferon-γcompletely attenuates eotaxin generation. (Miyamasu M.et al. Int. Immunol. 11 : 1001-4, 1999)
2) Dermal fibroblasts represent a major cellular source of eotaxin. (Miyamasu M.et al. Cytokine 11 : 751-8, 1999)
3) Level of eotaxin is increased in association with clinical parameters in induced sputum of asthmatic patients. (Yamada H.et al. Allergy 55 : 1-6, 2000)
4) Interferon-γ does not affect stability of eotaxin mRNA, indicating its inhibitory role at post-translational level. (Miyamasu, M.et al. manuscript in preparation)
5) Functional eosinophil CXCR4 is inducible in eosinophils under certain conditions. (Nagase et al. J.Immunol. 164 : 5935-43, 2000 ; Nagase et al. J.Allergy Clin. Immunol. 106 : 1132-9, 2000)
6) Bronchial epithelium of asthmatics intensely expresses a Th-2 specific chemokine thymus and activation-related chemokine (TARC). (Sekiya T.et al. J.Immunol. 165 : 2205-13, 2000)
Our results indicate that eotaxin represents a potential therapeutic target for allergic inflammation. Further study dealing molecular mechanisms underlying interferon-γ-mediated inhibition of eotaxin generation will facilitate the establishment of a novel strategy for treatment of allergic disorders.
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