| Project/Area Number |
07556066
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | Tokyo University of Agriculture and Technology |
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Principal Investigator |
MATSUDA Hiroshi Tokyo University of Agriculture and Technology, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (80145820)
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| Co-Investigator(Kenkyū-buntansha) |
TSUDZUKI Masaki Hiraoshima University, Faculty of Applied Biological Science, Associate Professo, 生物生産学部, 助教授 (70212058)
HIKASA Yoshiaki Tottori University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (30165071)
WATANABE Gen Tokyo University of Agriculture and Technology, Faculsy of Agriculture, Associat, 農学部, 助教授 (90158626)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥19,700,000 (Direct Cost: ¥19,700,000)
Fiscal Year 1997: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1996: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1995: ¥9,900,000 (Direct Cost: ¥9,900,000)
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| Keywords | mouse model / atopic dermatitis / mast cells / eosinophils / IgE / T cells / cytokines / atopy genes |
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| Research Abstract |
Atopic dermatitis (AD) is one of the most common skin diseases in children. However, the exact etiology has not been unclear. To further explore the pathogenesis and treatment of AD,NC mice tahat show spontanous development of AD-like skin lesions are very suitalble. In the present reseaarch project with NC mice, we investigated patholocial examination of AD-like skin lesions, immunologcial responses, and genetic analyzes. The obtained results are as follows :
1) IL-4 is a cytokine essetial for IgE synthesis of B cells was produced from activated mast cells and CD4 positive T cells infiltrated in the skin lesions.
2) Although there was no difference in the expression of CD40 on B cells between NC and BALB/c mice, B cells of NC mice produced much more IgE in the presence of IL-4 and soluble CD40 ligand and were more sensitive to IL-4, resulting in high tyrosin phsophorylation of JAK3.
3) Ceramide levels, important compounds for water permiability-barrier function and water-retention, decreased in NC mice, associated with reduction of sphingomyelinase activity and enhancement of ceramidase activity.
4) We concluded that development of the skin lesion was contrrolled by an autosomal recessive gene, the symbol derm ; IgE hyperproduction was regulataed by two autosomal recessive genes, the symbols ieh1 and ieh2.
5) FK 506 ointment suppressed all of the IL-4 production, IgE synthesis, infiltration of T cells and eosinophils, and degranulation of mast cells, suggesting that FK506 may be a usuful drug for AD.
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