TNF-α and Th2 Cytokines Induce Atopic Dermatitis-Like Features on Epidermal Differentiation Proteins and Stratum Corneum Lipids in Human Skin Equivalents
TNF-α and Th2 Cytokines Induce Atopic Dermatitis-Like Features on Epidermal Differentiation Proteins and Stratum Corneum Lipids in Human Skin Equivalents
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DOI：
10.1038/jid.2014.83
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发表时间：
2014-07-01
影响因子：
6.5
通讯作者：
Bouwstra, Joke A.
中科院分区：
文献类型：
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作者：
Danso, Mogbekeloluwa O.;van Drongelen, Vincent;Bouwstra, Joke A.
特应性皮炎(AD)是一种皮肤屏障功能受损的慢性炎症性皮肤病。在这种炎症性AD环境中，细胞因子上调，但细胞因子对AD皮肤屏障的作用尚不完全清楚。本研究旨在探讨Th2细胞因子(IL-4、IL-13、IL-31)和促炎性细胞因子(肿瘤坏死因子-α)对表皮形态发生、增殖、分化和角质层脂质性质的影响。为此，我们使用了莱顿表皮模型(LEM)，在该模型中，介质中添加了这些细胞因子。我们的结果表明，IL-4、IL-13、IL-31和TNF-α可诱导狼疮样变，增加角质形成细胞分泌TSLP，并改变LEM早期和晚期分化蛋白的表达。单独或与Th2细胞因子联合使用可降低长链游离脂肪酸(FFAs)和酯连接的欧米伽-羟基(EO)神经酰胺的水平，从而影响脂质组织。IL-31增加LIMs中的长链FFA，但降低EO神经酰胺的相对丰度。这些发现清楚地表明，补充肿瘤坏死因子-α和Th2细胞因子影响了表皮的形态发生和屏障功能。因此，这些LIMS显示出与AD皮肤中发现的相似的特征，可以作为筛选治疗AD的配方和药物的优秀工具。
Atopic dermatitis (AD) is a chronic inflammatory skin disease in which the skin barrier function is disrupted. In this inflammatory AD environment, cytokines are upregulated, but the cytokine effect on the AD skin barrier is not fully understood. We aimed to investigate the influence of Th2 (IL-4, IL-13, IL-31) and pro-inflammatory (tumor necrosis factor alpha (TNF-alpha)) cytokines on epidermal morphogenesis, proliferation, differentiation, and stratum corneum lipid properties. For this purpose, we used the Leiden epidermal model (LEM) in which the medium was supplemented with these cytokines. Our results show that IL-4, IL-13, IL-31, and TNF-alpha induce spongiosis, augment TSLP secretion by keratinocytes, and alter early and terminal differentiation-protein expression in LEMs. TNF-alpha alone or in combination with Th2 cytokines decreases the level of long chain free fatty acids (FFAs) and ester linked omega-hydroxy (EO) ceramides, consequently affecting the lipid organization. IL-31 increases long chain FFAs in LEMs but decreases relative abundance of EO ceramides. These findings clearly show that supplementation with TNF-alpha and Th2 cytokines influence epidermal morphogenesis and barrier function. As a result, these LEMs show similar characteristics as found in AD skin and can be used as an excellent tool for screening formulations and drugs for the treatment of AD.