Epithelial and Mesenchymal Cell Biology Type 2 Helper T-Cell Cytokines Induce Morphologic and Molecular Characteristics of Atopic Dermatitis in Human Skin Equivalent
Epithelial and Mesenchymal Cell Biology Type 2 Helper T-Cell Cytokines Induce Morphologic and Molecular Characteristics of Atopic Dermatitis in Human Skin Equivalent
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上皮和间充质细胞生物学 2 型辅助 T 细胞细胞因子诱导人类皮肤等效物特应性皮炎的形态和分子特征
DOI：
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
G. Tjabringa
中科院分区：
文献类型：
--
作者：
M. Kamsteeg;M. Bergers;R. D. Boer;P. Zeeuwen;S. Hato;J. Schalkwijk;G. Tjabringa
免疫系统和表皮都可能在特应性皮炎（AD）的发病机制中起重要作用。本研究的目的是开发一种人类皮肤等效模型，以受控的方式显示AD的形态学和分子特征。用2型辅助性T细胞（Th 2）细胞因子IL-4和IL-13刺激正常成人角质形成细胞产生的皮肤等效物，并研究表皮的形态学特征和基因表达。Th 2细胞因子诱导的细胞间水肿与在组织病理学分析和电子显微镜下观察到的病变AD中观察到的海绵样变化相似。此外，诱导已知在AD患者的表皮中特异性表达的基因，如CAII和NELL 2。相反，银屑病相关基因如弹性蛋白酶和hBD 2的表达没有改变。Th 2细胞因子引起角质形成细胞DNA断裂，这可以被半胱天冬酶抑制剂Z-VAD抑制，这表明诱导了凋亡。此外，在Th 2细胞因子刺激后，在角质形成细胞中观察到死亡受体Fas的上调。IL-4和IL-13诱导信号分子STAT 6的磷酸化。得出的结论是，本文所述的皮肤等效模型可用于研究AD的表皮方面和用于研究在角质形成细胞生物学水平起作用的药物。(Am J Pathol 2011，178：2091-2099; DOI：10.1016/j.ajpath.2011.01.037）
Both the immune system and the epidermis likely have an important role in the pathogenesis of atopic dermatitis (AD). The objective of the present study was to develop a human skin equivalent model exhibiting morphologic and molecular characteristics of AD in a controlled manner. Skin equivalents generated from normal adult human keratinocytes were stimulated with type 2 T-helper cell (Th2) cytokines IL-4 and IL-13, and morphologic features and gene expression of the epidermis were studied. Th2 cytokines induced intercellular edema similar to spongiotic changes observed in lesional AD as assessed at histopathologic analysis and electron microscopy. Furthermore, genes known to be specifically expressed in epidermis of patients with AD such as CAII and NELL2 were induced. In contrast, expression of psoriasis-associated genes such as elafin and hBD2 was not changed. Th2 cytokines caused DNA fragmentation in the keratinocytes, which could be inhibited by the caspase inhibitor Z-VAD, which suggests that apoptosis was induced. In addition, up-regulation of the death receptor Fas was observed in keratinocytes after Th2 cytokine stimulation. IL-4 and IL-13 induced phosphorylation of the signaling molecule STAT6. It was concluded that the skin equivalent model described herein may be useful in investigation of the epidermal aspects of AD and for study of drugs that act at the level of keratinocyte biology. (Am J Pathol 2011, 178:2091–2099; DOI: 10.1016/j.ajpath.2011.01.037)
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影响因子：
14.2
作者：
Nomura, L;Gao, B;Leung, DYM
通讯作者：
Leung, DYM
影响因子：
6.5
作者：
Lowes, Michelle A.;Kikuchi, Toyoko;Krueger, James G.
通讯作者：
Krueger, James G.
DOI：
10.1038/jid.2008.106
发表时间：
2009-01
期刊：
The Journal of investigative dermatology
影响因子：
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作者：
通讯作者：
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影响因子：
158.5
作者：
Ong, PY;Ohtake, T;Leung, DYM
通讯作者：
Leung, DYM