Kawakami Yuko, Yumoto Kenji, Kawakami Toshiaki
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Allergol Int. 2007 Dec;56(4):403-9. doi: 10.2332/allergolint.O-07-486. Epub 2007 Sep 1.
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.
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.
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.
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.
特应性皮炎是一种慢性或慢性复发性瘙痒性炎症性皮肤病。在过去三十年中，工业化国家特应性皮炎的发病率急剧上升。我们试图开发一种改进的方法来诱导特应性皮炎动物模型，并使用该模型评估Tec家族激酶抑制剂的疗效。
我们通过重复经皮应用屋尘螨变应原和金黄色葡萄球菌肠毒素B来治疗易患皮炎的近交系小鼠NC/Nga，以诱导类似特应性皮炎的皮肤病变。
我们建立了一种高效的方案来诱导NC/Nga小鼠出现皮肤病变，这些病变在组织学和免疫学上与人类特应性皮炎相似。与人类患者相似，皮炎诱导小鼠的血清IgE水平升高。与浸润免疫细胞在人类特应性皮炎发病机制中的作用一致，Tec家族激酶抑制剂土曲霉酸以及地塞米松可治疗皮肤病变。
我们建立了一种高效、高度可重复的方案来诱导NC/Nga小鼠出现皮肤病变，并成功应用该方案证明了土曲霉酸治疗皮肤病变的疗效。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并评估候选药物的疗效。
