| 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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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | DNA vaccine / Atonic dermatitis / dominant-negative / IL-4 / IL-13 / IL-18 / scratching / gene therapy / DNAワクチン / ドミナントネガティブ変異体 / 受容体拮抗薬 / マウスモデル / サイトカイン / アレルギー / 遺伝子導入 / モデルマウス |
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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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