Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis:: Structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges
Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis:: Structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges
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DOI：
10.1038/sj.jid.5701011
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发表时间：
2008-01-01
影响因子：
6.5
通讯作者：
Elias, Peter M.
中科院分区：
文献类型：
--
作者：
Man, Mao-Qiang;Hatano, Yutaka;Elias, Peter M.
特应性皮炎(AD)是一种慢性皮肤病，具有与慢性变态反应性接触性皮炎(ACD)相似的临床、组织学和免疫学特征。AD显示以Th2细胞为主的炎性浸润，血清IgE水平升高，通透性屏障异常，金黄色葡萄球菌定植。据报道，反复的半抗原激发会产生类Th2超敏反应(类Th2 HR)。在这里，恶唑酮(Ox)对无毛小鼠的9-10次挑战也产生了慢性Th2样HR。通透性屏障功能异常，分化蛋白丝状蛋白、氯化蛋白和总蛋白表达异常。CRTH阳性的Th2为主的炎性细胞浸润，IL-4表达增加，血清IgE水平明显升高。屏障异常与角质层神经酰胺含量降低和板层小体分泌受损有关，导致板层膜异常，就像人类AD一样。此外，与人类AD一样，Ox攻击后SC中的表皮丝氨酸蛋白酶活性增加，两个板层体源性抗菌肽JRIMP和MBD3的表达下降，与AD中它们的人类同源物减少的情况相平行。因此，Ox对正常小鼠皮肤的多次挑战会产生一种慢性Th2样HR，具有人类AD的多种特征。由于其重复性、可预测性和低成本，该模型可用于评估AD的发病机制和潜在的治疗方法。
Atopic dermatitis (AD) is a chronic dermatosis bearing clinical, histological, and immunologic similarities to chronic allergic contact dermatitis (ACD). AD shows a Th2 cell-dominant inflammatory infiltrate, elevated serum IgE levels, a permeability barrier abnormality, and Staphylococcus aureas colonization. Repeated hapten challenges reportedly produce a Th2-like hypersensitivity reaction (Th2-like HR). Here, 9-10 challenges with oxazolone (Ox) to hairless mice also produced a chronic Th2-like HR. Permeability barrier function and expression of differentiation proteins, filaggrin, loricrin, and involucrin, became abnormal. CRTH-positive Th2-dominant inflammatory infiltrate, with increased IL-4 expression, and a large increase in serum IgE levels were observed. The barrier abnormality was associated with decreased stratum corneum (SC) ceramide content and impaired lamellar body secretion, resulting in abnormal lamellar membranes, as in human AD. Furthermore, as in human AD, epidermal serine protease activity in SC increased and expression of two lamellar body-derived antimicrobial peptides, CRAMP and mBD3, declined after Ox challenges, paralleling the decrease of their human homologues in AD. Thus, multiple Ox challenges to normal murine skin produce a chronic Th2-like HR, with multiple features of human AD. Because of its reproducibility, predictability, and low cost, this model could prove useful for evaluating both pathogenic mechanisms and potential therapies for AD.