2003 Fiscal Year Final Research Report Summary
A study for atopic dermatitis controlledby Caspase-1 and IL-18
| Project/Area Number |
13470171
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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 |
Dermatology
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| Research Institution | Mie University |
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Principal Investigator |
MIZUTANI Hitoshi Mie University, Faculty of Medicine, Professor, 医学部, 教授 (30115737)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANISHI Kenji Hyogo College of Medicine, Professor, 医学部, 教授 (60172350)
TSUTSUI Hiroko Hyogo College of Medicine, Associate Professor, 医学部, 助教授 (40236914)
YASUTOMI Yasuhiro Mie University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (90281724)
YAMANISHI Kiyofumi Hyogo College of Medicine, Professor, 医学部, 教授 (10182586)
ISODA Kenichi Mie University, Faculty of Medicine, Research Associate, 医学部, 助手 (50262994)
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| Project Period (FY) |
2001 – 2003
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| Keywords | IL-18 / IL-1 / hiatamine / caspase / Atopic dermatitis / Innate immunity / Innate atopy / psoriasis |
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| Research Abstract |
We have established two transgenic mice (skin specifically caspase-1 and IL-18 overexpressed mice), and these mice developed persistent dermatitis similar to the human atopic dermatitis (AD). The skin and systemic immune systems of these mice were allergic type shifted to Th2 conditions, secreting IL-18, IL-4, IL-5 and IL-10. Dermal mastocytosis and hyper histaminemia resulted in intensive scratching behaviour as a characteristic model for atopic dermatitis, and significant elevation of serum IgE levels. IgE-/-Caspase-1Tg persisted AD type skin lesions, but extermination of IL-18 completely suppressed development of the skin lesions, which strongly supported IL-18 dependency of this dermatitis. Because these lesions were independent from the exogenous allergens, we proposed a new concept as innate type atopy in contrast to the allergen dependent IgE mediated atopy. We successfully treated the skin manifestations of the caspase-1Tg using BCG vaccination with suppressed IL-18 production. We also developed Stat6-/-caspase-1Tg, which developed skin lesions mimic pustular psoriasis without Th2 shift. These studies revealed importance of the percutaneous IL-18secretion in both of Th2 type AD and Th1 type psoriasis.
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Research Products
(23 results)
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[Publications] Konishi, H., Tsutsui, H., Murakami, T., Yamanaka, K., Mizutani, H., et al.: "IL-18 contributes to the spontaneous development of atopic dermatitis-like skin lesion in dependently of IgE/stat6 under specific pathogen-free conditions."Proc.Natl.Acad.Sci.USA. 99. 11345 (2002)
Description
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