2007 Fiscal Year Final Research Report Summary
Effects of the mutant cytokine therapy in atopic dermatitis
| Project/Area Number |
18591242
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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 |
Dermatology
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| Research Institution | Mie University |
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Principal Investigator |
MIZUTANI Hitoshi Mie University, Postgraduate School of Medicine, Department of Dermatology, Professor (30115737)
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| Co-Investigator(Kenkyū-buntansha) |
YAMANAKA Keiichi Mie University Hospital, Department of Dermatology, Lecturer (70314135)
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| Project Period (FY) |
2006 – 2007
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| Keywords | DNA vaccine / Atonic dermatitis / dominant-negative / IL-4 / IL-13 / IL-18 / scratching / gene therapy |
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| Research Abstract |
To express cytokine DNA in mast cells, IL-4 ligated to a mast cell specific promoter was injected to mouse eggs. No obvious transferred IL-4 was detected in the born mice and their offspring. Therefore, we switched strategy to express mutant IL-4 species by transgenic system to vaccination to mouse.
Mice with Th2 type chronic dermatitis were established with serially topical application of hapten. These mice were treated with DNA vaccine coding IL-4, dominant-negative decoy IL-4 or dominant-negative decoy IL-4/IL-13. Th2 type dermatitis was successfully suppressed dominant negative IL-4/IL-13 decoy vaccination, and limited effects with IL-4 decoy. IL-4 agonist or mock FNA showed no effects. This experiment revealed dominant-negative IL-4/IL-13 decoy DNA is a potent therapeutic tool for atopic dermatitis.
To evaluate the itching sensation of model mouse, we established a measuring system of scratching movement by acoustic analysis.This system declared invisibly rapid scratching behavior of the atopic dermatitis (AD) model mouse. Then, this system revealed effective suppression of the scratching counts of AD mouse with oral administration of anti-histamine dose dependently.
To know the roles of mast cells in AD, the mast cell derived enzymes were evaluated in cytokine activation. The human mast cell chymase processed IL-18 successfully and generated an active species. This revealed importance of mast cells and their chymase discharge in AD skin lesions.
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[Presentation] アトピー性皮膚炎とIL-182006
Author(s)
今井康友, 水谷 仁, 他計10名
Organizer
第71回日本インターフェロン・サイトカイン学会
Place of Presentation
西宮
Year and Date
20060707-08
Description
「研究成果報告書概要(和文)」より
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[Presentation] Atopic dermatitis and IL-182006
Author(s)
Imai, Y., Mizutani, H., et. al.
Organizer
71th annual meeting of Japanese society of interferon and cytokine research
Place of Presentation
Nishinomiya
Year and Date
20060707-08
Description
「研究成果報告書概要(欧文)」より
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