Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6
Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6
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DOI：
10.1016/j.clim.2007.11.006
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发表时间：
2008-03-01
影响因子：
8.6
通讯作者：
Howell, Michael D.
中科院分区：
文献类型：
--
作者：
Kim, Byung Eui;Leung, Donald Y. M.;Howell, Michael D.
特应性皮炎(AD)的特征是皮肤屏障有缺陷，导致过敏原和病原体渗透增加。洛丽蛋白(Loricrin，Lor)和总状蛋白(Venducrin，IVL)是皮肤屏障形成和完整性的重要蛋白质。在这项研究中，我们发现AD患者受累(LOR：P<；0.001；IVL：P<；0.001)和非受累(LOR：P<；0.001；IVL：P<；0.001)皮肤中LOR和IVL的基因和蛋白表达显著低于健康人皮肤。利用原代角质形成细胞，我们进一步证明了IL-4和IL-13--在AD患者皮肤中过度表达--对角质形成细胞LOR和IVL表达的下调作用。此外，信号转导和转录激活因子(STAT)-6转基因小鼠的皮肤活检组织中LOR和IVL的表达和产生不足。本研究提示Th2细胞因子通过STAT-6依赖机制抑制LOR和IVL的表达。(C)2007 Elsevier Inc.Alt版权所有。
Atopic dermatitis (AD) is characterized by a defective skin barrier which allows increased allergen and pathogen penetration. Loricrin (LOR) and involucrin (IVL) are proteins important for skin barrier formation and integrity. In this study, we demonstrate that the gene and protein expression of LOR and IVL is significantly decreased in involved (LOR: p < 0.001; IVL: p < 0.001) and uninvolved (LOR: p < 0.001; IVL: p < 0.001) skin of AD subjects, as compared to skin from healthy subjects. Using primary keratinocytes, we further demonstrate the downregulatory effect of IL-4 and IL-13 - which are over-expressed in the skin of AD patients - on LOR and IVL expression in keratinocytes. Additionally, skin biopsies from signal transducer and activator of transcription (STAT)-6 transgenic mice were deficient in the expression and production of LOR and IVL. This study suggests that Th2 cytokines inhibit expression of LOR and IVL through a STAT-6 dependent mechanism. (c) 2007 Elsevier Inc. Alt rights reserved.