Catania A, Colombo G, Rossi C, Carlin A, Sordi A, Lonati C, Turcatti F, Leonardi P, Grieco P, Gatti S
Center for Preclinical Investigation, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano 20122, Italy.
ScientificWorldJournal. 2006 Oct 2;6:1241-6. doi: 10.1100/tsw.2006.227.
The natural antimicrobial peptides are ancient host defense effector molecules, present in organisms across the evolutionary spectrum. Several properties of alpha-melanocyte stimulating hormone (alpha-MSH) suggested that it could be a natural antimicrobial peptide. Alpha-MSH is a primordial peptide that appeared during the Paleozoic era, long before adaptive immunity developed and, like natural antimicrobial molecules, is produced by barrier epithelia, immunocytes, and within the central nervous system. alpha-MSH was discovered to have antimicrobial activity against two representative pathogens, Staphylococcus aureus and Candida albicans. The candidacidal influences of alpha-MSH appeared to be mediated by increases in cell cyclic adenosine monophosphate (cAMP). The cAMP-inducing capacity of alpha-MSH likely interferes with the yeast's own regulatory mechanisms of this essential signaling pathway. It is remarkable that this mechanism of action in yeast mimics the influences of alpha-MSH in mammalian cells in which the peptide binds to G-protein-linked melanocortin receptors, activates adenylyl cyclase, and increases cAMP. When considering that most of the natural antimicrobial peptides enhance the local inflammatory reaction, the anti-inflammatory and antipyretic effects of alpha-MSH confer unique properties to this molecule relative to other natural antimicrobial molecules. Synthetic derivatives, chemically stable and resistant to enzymatic degradation, could form the basis for novel therapies that combine anti-inflammatory and antimicrobial properties.
天然抗菌肽是古老的宿主防御效应分子，存在于整个进化谱系的生物体中。α-黑素细胞刺激素（α-MSH）的若干特性表明它可能是一种天然抗菌肽。α-MSH是一种在古生代出现的原始肽，远在适应性免疫发展之前，并且与天然抗菌分子一样，由屏障上皮细胞、免疫细胞以及在中枢神经系统内产生。已发现α-MSH对两种代表性病原体金黄色葡萄球菌和白色念珠菌具有抗菌活性。α-MSH的杀念珠菌作用似乎是由细胞环磷酸腺苷（cAMP）增加介导的。α-MSH的cAMP诱导能力可能干扰酵母自身对这一重要信号通路的调节机制。值得注意的是，这种在酵母中的作用机制模仿了α-MSH在哺乳动物细胞中的作用，在哺乳动物细胞中该肽与G蛋白偶联的黑皮质素受体结合，激活腺苷酸环化酶并增加cAMP。鉴于大多数天然抗菌肽会增强局部炎症反应，α-MSH的抗炎和解热作用赋予了该分子相对于其他天然抗菌分子的独特特性。化学稳定且抗酶降解的合成衍生物可为结合抗炎和抗菌特性的新型疗法奠定基础。
