“防御素”是先天免疫系统的关键“效应子”分子，保护宿主不受感染性微生物侵害并决定粘膜表面上微生物群的组成。“人β-防御素-1” (hBD-1)是同类中最著名的肽之一，由几乎所有的人上皮点表达，但以前的研究工作表明，它与其他“防御素”相比抗菌活性低。现在，Jan Wehkamp及其同事发现，在与结肠末端相似的还原条件下，hBD-1表现出针对潜在病原体白色念珠菌、双岐杆菌和乳酸菌的强力抗菌性。试管实验证据表明，“硫氧还蛋白”是最有可能掩蔽hBD-1在小肠上皮中抗菌活性的还原剂。（生物谷Bioon.com）
生物谷推荐原文出处：
Nature doi:10.1038/nature09674
Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1
Bjoern O. Schroeder,Zhihong Wu,Sabine Nuding,Sandra Groscurth,Moritz Marcinowski,Julia Beisner,Johannes Buchner,Martin Schaller,Eduard F. Stange& Jan Wehkamp
Human epithelia are permanently challenged by bacteria and fungi, including commensal and pathogenic microbiota1, 2. In the gut, the fraction of strict anaerobes increases from proximal to distal, reaching 99% of bacterial species in the colon3. At colonic mucosa, oxygen partial pressure is below 25% of airborne oxygen content, moreover microbial metabolism causes reduction to a low redox potential of ?200?mV to –300?mV in the colon4. Defensins, characterized by three intramolecular disulphide-bridges, are key effector molecules of innate immunity that protect the host from infectious microbes and shape the composition of microbiota at mucosal surfaces5, 6, 7, 8. Human β-defensin 1 (hBD-1) is one of the most prominent peptides of its class but despite ubiquitous expression by all human epithelia, comparison with other defensins suggested only minor antibiotic killing activity9, 10. Whereas much is known about the activity of antimicrobial peptides in aerobic environments, data about reducing environments are limited. Herein we show that after reduction of disulphide-bridges hBD-1 becomes a potent antimicrobial peptide against the opportunistic pathogenic fungus Candida albicans and against anaerobic, Gram-positive commensals of Bifidobacterium and Lactobacillus species. Reduced hBD-1 differs structurally from oxidized hBD-1 and free cysteines in the carboxy terminus seem important for the bactericidal effect. In vitro, the thioredoxin (TRX) system11 is able to reduce hBD-1 and TRX co-localizes with reduced hBD-1 in human epithelia. Hence our study indicates that reduced hBD-1 shields the healthy epithelium against colonisation by commensal bacteria and opportunistic fungi. Accordingly, an intimate interplay between redox-regulation and innate immune defence seems crucial for an effective barrier protecting human epithelia
