Characterization of MC903 induced Atopic Dermatitis‐like skin inflammation in mice
Characterization of MC903 induced Atopic Dermatitis‐like skin inflammation in mice
复制标题
MC903 诱导小鼠特应性皮炎样皮肤炎症的表征
DOI：
10.1096/fasebj.2020.34.s1.09550
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
S. McGaraughty
中科院分区：
文献类型：
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作者：
K. Chu;Z. Su;J. Wetter;M. Namovic;L. Leys;Yibing Wang;P. Honore;S. McGaraughty
特应性皮炎（AD）是一种慢性炎症性皮肤病，影响全世界的成人和儿童。AD的症状，如复发性干燥、鳞状病变和强烈瘙痒，可能成为患者及其护理人员的巨大负担。需要动物模型来更好地理解AD的病理生理学和评估新的治疗方法。据报道，在小鼠皮肤上局部应用MC 903（卡泊三醇）可捕获与AD相关的关键特征。在本研究中，我们对MC 903诱导的小鼠耳部皮肤炎症进行了全面表征。11天的时间过程显示皮肤增厚早在第4天开始，并显著进展至第10天。这种慢性表现为耳部皮肤经表皮水分流失增加。组织学上，观察到血管增生、海绵状增生、强烈的免疫细胞浸润和表皮增生。这些动物也表现出类似的行为。2型和其他炎性细胞因子如IL-4、IL-5、IL-31、TSLP（第4天达到峰值）、IL-1β、IFNγ、TNFα的皮肤表达通常在第7天升高，并进一步升高至第10天。大多数这些终点通过给予选择性JAK 1抑制剂（ABT-317）或类固醇（地塞米松）而减弱。这些观察结果进一步理解了MC 903作为AD临床前模型的实用性。
Atopic Dermatitis (AD) is a chronic inflammatory skin disease that affects both adults and children worldwide. Symptoms of AD, such as recurrent dry, scaly lesions and intensive pruritus, can become an enormous burden to patients and their caregivers. Animal models are needed to better understand the pathophysiology of AD and for evaluating novel therapeutics. Topically applying MC903 (calcipotriol) on mouse skin has been reported to capture key features associated with AD. In the current study, we conducted a comprehensive characterization of MC903 induced ear skin inflammation in the mouse. An 11 day time course revealed skin thickening starting as early as day 4 and significantly progressing up to day 10. This chronicity was mirrored by increased transepidermal water loss in the ear skin. Histologically, hypervascularization, spongiosis, strong immune cell infiltration and epidermal hyperplasia were observed. The animals also manifested pruritic behaviors. The skin expression of Type 2 and other inflammatory cytokines such as IL‐4, IL‐5, IL‐31, TSLP (peak day 4), IL‐1β, IFNγ, TNFα were typically elevated by day 7 and further increased to day 10. Most of these endpoints were attenuated by administration of a selective JAK1 inhibitor (ABT‐317) or a steroid (Dexamethasone). The observations further the understanding of the utility of MC903 as a preclinical model for AD.