Peric M, Koglin S, Ruzicka T, Schauber J
Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität München, München, Germany.
Dtsch Med Wochenschr. 2009 Jan;134(1-2):35-8. doi: 10.1055/s-0028-1105888. Epub 2008 Dec 17.
The human skin is constantly exposed to microbial pathogens but infections only rarely occur. Innate cutaneous immunity is a primary system for protection against infection, and antimicrobial peptides (AMPs) expressed in skin are essential defence molecules. The AMPs include molecules such as the defensins that were first characterized for their antimicrobial properties as well as other peptides and proteins first known for their activity as chemokines, enzymes, enzyme inhibitors and neuropeptides. Cathelicidins are unique AMPs that act as defensive and signalling molecules. Two different pathways are involved in this function: cathelicidins have direct antimicrobial activity and they also initiate a host of cellular responses in cytokine release, inflammation and angiogenesis. Several skin diseases are associated with cathelicidin dysfunction. In atopic eczema, for example, cathelicidin expression is suppressed, whereas in rosacea cathelicidin peptides are abnormally processed to forms that induce cutaneous inflammation and a vascular response. In psoriasis cathelicidin peptide converts self-DNA to a potent stimulus in an autoinflammatory cascade. Current studies have unexpectedly identified vitamin D3 as a major factor for the regulation of cathelicidin expression. This finding may provide new strategies in the management of infectious and inflammatory diseases of the skin by targeting control of the expression and function of cathelicidin and other AMPs.
人类皮肤持续暴露于微生物病原体,但感染却很少发生。先天性皮肤免疫是抵御感染的主要系统,皮肤中表达的抗菌肽(AMPs)是至关重要的防御分子。抗菌肽包括诸如防御素等分子,防御素最初因其抗菌特性而被鉴定,以及其他最初因其作为趋化因子、酶、酶抑制剂和神经肽的活性而为人所知的肽和蛋白质。杀菌肽是独特的抗菌肽,兼具防御和信号传导分子的作用。该功能涉及两种不同途径:杀菌肽具有直接抗菌活性,还能引发一系列细胞反应,包括细胞因子释放、炎症和血管生成。几种皮肤疾病与杀菌肽功能障碍有关。例如,在特应性皮炎中,杀菌肽表达受到抑制,而在酒渣鼻中,杀菌肽肽异常加工形成诱导皮肤炎症和血管反应的形式。在银屑病中,杀菌肽肽在自身炎症级联反应中将自身DNA转化为强效刺激物。目前的研究意外地发现维生素D3是调节杀菌肽表达的主要因素。这一发现可能通过靶向控制杀菌肽和其他抗菌肽的表达及功能,为皮肤感染性和炎症性疾病的治疗提供新策略。