| Project/Area Number |
07044184
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Tokyo University of Agriculture and Technology |
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Principal Investigator |
MATSUDA Hiroshi Faculty of Agriculture, Tokyo University of Agriculture Technology, 農学部, 助教授 (80145820)
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| Co-Investigator(Kenkyū-buntansha) |
GEBA Gregory P Yale University School of Medicine, School of Medicine, 助教授
ASKENASE Philip W Yale University School of Medicine, School of Medicine, 教授
ARAI Katsuhiko Faculty of Agriculture, Tokyo University of Agriculture and Technology Assistant, 農学部, 助教授 (60175940)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | mouse model / atopy / dermatitis / mast cells / eosinophils / lymphocytes / cytokines / IgE / lgE |
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| Research Abstract |
Atopic dermatitis is one of the common skin diseases in children with an individual or family history of allergic diseases, and is frequently associated with elevated serum levels of IgE antibodies against many kinds of inhaled allergenes. Epidemiological reports suggest that the onset of atopic dermatitis is influenced by environmental factors (s) and its prevalence is still increasing. Although great attention of atopic dermatitis has been focused on the pathogenesis, the exact etiology of atopic dermatitis has been unclear. Establishment of a suitable animal model is definitely of great importance in elucidation of the pathogenesis and to develop new approaches to the therapy. We have found that skin lesions, which were clinically and histologically very similar to human atopic dermatitis, spontaneously appeared on the face, neck, ears, and dorsal skin of inbred NC/Nga mice when they were raised in non-sterile (conventional) circumstances, but not under specific pathogen-free conditions. Plasmalevels of total IgE in conventional NC/Nga mice were markedly elevated from 8 weeks of age, correlating with clinical skin severity of dermatitis. Immunohistochemical examination of the skin lesion showed increased numbers of mast cells and CD4^+ T cells comtaining IL-4 necessary for IgE synthesis. Transplantation of skin with dermatitis from conventional NC/Nga mice resulted in a significant increase in plasma levels of total IgE in recipient specific pathogen-free NC/Nga mice. The results presented suggest that NC/Nga mice are a suitable model for certain aspects of human atopic dermatitis and that their dermatitis with IgE hyperproduction is influenced by some environmental factor (s), and is due, at least in part to IL-4 released by mast cells and CD4^+T cells in the affected skin. Thus, NC/Nga mice are a useful model to investigate the pathogenesis of atopic dermatitis, and to develop more effective therapy for atopic dermatitis.
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