An improved mouse model of atopic dermatitis and suppression of skin lesions by an inhibitor of Tec family kinases.
An improved mouse model of atopic dermatitis and suppression of skin lesions by an inhibitor of Tec family kinases.
复制标题
DOI：
10.2332/allergolint.o-07-486
复制
发表时间：
2007-12-01
期刊：
影响因子：
--
通讯作者：
Kawakami, Toshiaki
中科院分区：
文献类型：
--
作者：
Kawakami, Yuko;Yumoto, Kenji;Kawakami, Toshiaki
背景：特应性皮炎是一种慢性或慢性复发的瘙痒性炎症性皮肤病。在过去的三十年里，在工业化国家，特应性皮炎的发病率急剧增加。我们试图开发一种改进的方法来诱导特应性皮炎的动物模型，并用它来评价Tec家族激酶抑制剂的疗效。方法：通过重复表面应用屋尘螨变应原和葡萄球菌肠毒素B诱导特应性皮炎样皮肤皮损，对易患皮炎的近交系小鼠NC/Nga进行治疗。结果：我们建立了一种高效的方法，在组织学和免疫学上与人类特应性皮炎相似的NC/Nga小鼠诱导皮肤病变。与人类患者相似，皮炎诱导的小鼠血清IgE水平也升高。与浸润性免疫细胞在人类特应性皮炎发病机制中的作用一致，皮肤病变可用Tec家族激酶抑制剂土酸和地塞米松治疗。结论：我们建立了一种高效、高重复性的皮肤病变诱导方法，并成功地应用于显示土酸对皮肤病变的治疗效果。这种特应性皮炎小鼠模型将有助于研究特应性皮炎的发病过程和评估候选药物的疗效。
BACKGROUND: Atopic dermatitis is a chronic or chronically relapsing, pruritic inflammatory skin disease. The incidence of atopic dermatitis has dramatically increased during the past three decades in industrialized countries. We attempted to develop an improved method to induce an animal model of atopic dermatitis and to use it to evaluate the efficacy of a Tec family kinase inhibitor.METHODS: We treated dermatitis-prone inbred mice, NC/Nga, by repetitive epicutaneous applications of a house dust mite allergen and staphylococcal enterotoxin B to induce atopic dermatitis-like skin lesions.RESULTS: We established a highly efficient protocol to induce skin lesions in NC/Nga mice, which were histologically and immunologically similar to human atopic dermatitis. Similar to human patients, serum IgE levels were increased in dermatitis-induced mice. Consistent with the proposed roles of infiltrated immune cells in the pathogenesis of human atopic dermatitis, skin lesions were treatable with terreic acid, an inhibitor of Tec family kinases, as well as dexamethasone.CONCLUSIONS: We established a highly efficient, highly reproducible protocol to induce skin lesions in NC/Nga mice and successfully applied it to show the efficacy of terreic acid in treating skin lesions. This mouse model of atopic dermatitis will be useful to study the pathogenetic processes of atopic dermatitis and to evaluate the efficacy of drug candidates.