Waking the wimp Redox-modulation activates human beta-defensin 1
Waking the wimp Redox-modulation activates human beta-defensin 1
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DOI：
10.4161/gmic.2.4.17692
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发表时间：
2011-01-01
期刊：
影响因子：
12.2
通讯作者：
Wehkamp, Jan
中科院分区：
文献类型：
--
作者：
Schroeder, Bjoern O.;Stange, Eduard F.;Wehkamp, Jan
抗微生物肽是先天免疫系统的关键参与者，并形成抵抗微生物感染的主要屏障。在人类中，产生几类抗微生物肽，包括防御素。这些小的阳离子肽显示出对细菌、一些真菌和一些病毒的广谱抗微生物活性。防御素的特征在于通过三个二硫桥连接的六个保守的半胱氨酸残基。根据连接模式，人防御素被分类为α-或β-防御素。人β-防御素1（Human beta-defensin 1，hBD-1）由上皮细胞组成性表达，但与其它抗菌肽相比，hBD-1的抗菌活性较低，我们最近发现，hBD-1的三个二硫键被还原后，其抗菌活性大大增强。还原可以通过还原环境进行，因为它存在于人体肠道，口腔和其他部位的部分，或通过硫氧还蛋白系统酶促进行，硫氧还蛋白系统是主要的氧化还原调节剂之一。还原型hBD-1能够杀死人类正常植物群的革兰氏阳性厌氧菌以及机会致病性真菌，而氧化肽不显示针对这些微生物的活性。在此，我们提供了有关减少hBD-1的额外数据，并讨论了我们的研究结果的生物学背景。
A ntimicrobial peptides are key players of the innate immune system and form a primary barrier against infection by microorganisms. In humans, several classes of antimicrobial peptides are produced, including the defensins. These small, cationic peptides show broad spectrum antimicrobial activity against bacteria, some fungi and some viruses. Defensins are characterized by six conserved cysteine residues which are connected via three disulphide bridges. Depending o n the pattern of connectivity, human defensins are either classified as alpha- or beta-defensins. Human beta-defensin 1 (hBD-1) is constitutively expressed by epithelia, but in comparison with other antimicrobial peptides the antimicrobial activity of hBD-1 was comparably low.We recently found that after reduction of hBD-1's three disulphide bonds its antimicrobial activity is strongly enhanced. Reduction can be either performed by a reducing environment, as it is present in parts of the human intestine, the oral cavity and other locations, or enzymatically by the thioredoxinsystem, which is one of the major redox regulators. Reduced hBD-1 is able to kill Gram-positive anaerobic bacteria of the human normal flora as well as an opportunistic pathogenic fungus, whereas the oxidized peptide does not show activity against these microorganisms. Herein we provide additional data about reduced hBD-1 and discuss the biological context of our findings.