Development of atopic dermatitis in mice transgenic for human apolipoprotein C1
Development of atopic dermatitis in mice transgenic for human apolipoprotein C1
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DOI：
10.1038/sj.jid.5701182
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发表时间：
2008-05-01
影响因子：
6.5
通讯作者：
Oranje, Arnold P.
中科院分区：
文献类型：
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作者：
Nagelkerken, Lex;Verzaal, Perry;Oranje, Arnold P.
在肝脏和皮肤中转基因表达人载脂蛋白C1（APOC 1）的小鼠血清胆固醇、甘油三酯和游离脂肪酸水平显著升高，表明脂质代谢紊乱。重要的是，这些小鼠显示出皮肤屏障功能紊乱，从增加的经表皮水分损失中可以看出，并且自发地出现皮炎症状，包括鳞屑、苔藓样变、表皮脱落和瘙痒。组织学分析显示表皮增厚和海绵状组织增生增加，同时真皮中炎性细胞（嗜酸性粒细胞、中性粒细胞、肥大细胞、巨噬细胞和CD 4 + T细胞）数量增加。此外，受影响的小鼠具有增加的血清IgE水平，并且在真皮中显示丰富的IgE（+）肥大细胞。通过局部应用亲脂性软膏恢复皮肤屏障功能，可实现疾病的部分抑制。此外，皮质类固醇治疗抑制了这些小鼠中特应性皮炎的发展。APOC 1（+/+）小鼠的这些发现强调了皮肤屏障完整性在特应性皮炎发病机制中的作用。
Mice with transgenic expression of human apolipoprotein C1 (APOC1) in liver and skin have strongly increased serum levels of cholesterol, triglycerides, and free fatty acids, indicative of a disturbed lipid metabolism. Importantly, these mice display a disturbed skin barrier function, evident from increased transepidermal water loss, and spontaneously develop symptoms of dermatitis including scaling, lichenification, excoriations, and pruritus. Histological analysis shows increased epidermal thickening and spongiosis in conjunction with elevated numbers of inflammatory cells (eosinophils, neutrophils, mast cells, macrophages, and CD4+ T cells) in the dermis. In addition, affected mice have increased serum levels of IgE and show abundant IgE(+) mast cells in the dermis. Partial inhibition of disease could be achieved by restoration of the skin barrier function with topical application of a lipophilic ointment. Furthermore, the development of atopic dermatitis in these mice was suppressed by corticosteroid treatment. These findings in APOC1(+/+) mice underscore the role of skin barrier integrity in the pathogenesis of atopic dermatitis.