High-Glucose Environment Inhibits p38MAPK Signaling and Reduces Human β-3 Expression in Keratinocytes
High-Glucose Environment Inhibits p38MAPK Signaling and Reduces Human β-3 Expression in Keratinocytes
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DOI：
10.2119/molmed.2010.00091
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发表时间：
2011-07-01
影响因子：
5.7
通讯作者：
Chen, Gwo-Shing
中科院分区：
文献类型：
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作者：
Lan, Cheng-Che E.;Wu, Ching-Shuang;Chen, Gwo-Shing
糖尿病的特征是血浆葡萄糖升高和皮肤感染率增加。改变的免疫反应被认为是导致这种普遍的并发症的原因，这涉及微生物的入侵。在这项研究中，我们探讨了高葡萄糖环境对天然免疫的角质形成细胞的β防御素-3（BD 3）使用在体内和体外模型的影响。我们的研究结果表明，糖尿病大鼠的皮损周围皮肤未能显示增强BD 3表达创伤后。此外，高糖处理降低了培养的人角质形成细胞的人BD 3（hBD 3）表达。这种致病过程涉及p38 MAPK信号传导的抑制，这是由晚期糖基化终产物形成增加引起的事件。另一方面，培养的角质形成细胞的Toll样受体-2的表达和功能没有显着影响高糖处理。总之，高葡萄糖条件抑制表皮角质形成细胞的BD 3表达，这反过来又导致与糖尿病创伤相关的感染的频繁发生。(C)2011年费恩斯坦医学研究所，www.feinsteininstitute.org
Diabetes mellitus is characterized by elevated plasma glucose and increased rates of skin infections. Altered immune responses have been suggested to contribute to this prevalent complication, which involves microbial invasion. In this study we explored the effects of a high-glucose environment on the innate immunity of keratinocytes by focusing on beta defensin-3 (BD3) using in vivo and in vitro models. Our results demonstrated that the perilesional skins of diabetic rats failed to show enhanced BD3 expression after wounding. In addition, high-glucose treatment reduced human BD3 (hBD3) expression of cultured human keratinocytes. This pathogenic process involved inhibition of p38MAPK signaling, an event that resulted from increased formation of advanced glycation end products. On the other hand, toll-like receptor-2 expression and function of cultured keratinocytes were not significantly affected by high-glucose treatment. In summary, high-glucose conditions inhibited the BD3 expression of epidermal keratinocytes, which in turn contributed to the frequent occurrences of infection associated with diabetic wounding. (C) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org