| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
In allergic diseases, allergen specific Th2 cells are preferentially differentiated and play central roles on the formation of IgE responsiveness, organ hyper-reactivity and allergic inflammation. In this study what determinants might be responsible for such Th2 differentiation was asked.
The expression of cytokine and polymorphisms of candidate genes, which might cause preferential Th2 differentiation were examined. Analyses of gene polymorphisms including 5"IL-4 regulatory region, IL-4 receptor (R) and b2-adrenoceptor (ADR) genes in the patients with allergic diseases and controls showed that IL-4R-50Val/Ile was significantly associated with allergic diseases (odds ratio 2.3). In addition, combinational analysis of polymorphisms (IL-4R-50 and b2-ADR-16Arg/Gly) revealed that the odds ratio was 5.8. IL-18, a cytokine, recently found to possess an activity of Th2 induction, directly functioned activated eosinophils, resulting in enhancement of IL-8 production. Both in the patients with a
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topic dermatitis (AD) and in the AD model mouse, NC/Nga, serum levels of IL-18 were elevated. Continuous injection of anti-IL-18 Ab exacerbated skin lesions, however. Further studies were required to evaluate roles of IL-18 on atopic dermatitis. One polymorphism in human IL-18 exon gene (105A/C) was found and its significance remained unknown at the present time.
The clinical study testing efficacy of one folk remedy on the patients with AD prompted us to examine anti-allergic substances in the remedy. Persimmon leaf extract and its major ingredient, astragalin, a flavonol inhibit histamine release from basophils and oral administration of these substances strikingly inhibit development of dermatitis, IgE elevation and transepidermal water loss in NC/Nga mice. In addition, some kinds of flavonoids showed an inhibitory activity of expression of Th2 cytokines (IL-4, IL-5, IL-13) by activated basophils. These studies raised a possibility that these anti-allergic substances might to be alternative or complementary medicine. Less
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