Precursor Processing of Human Defensin-5 Is Essential to the Multiple Functions in vitro and in vivo
Precursor Processing of Human Defensin-5 Is Essential to the Multiple Functions in vitro and in vivo
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DOI：
10.1159/000242114
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发表时间：
2010-01-01
影响因子：
5.3
通讯作者：
Kohgo, Yutaka
中科院分区：
文献类型：
--
作者：
Ishikawa, Chisato;Tanabe, Hiroki;Kohgo, Yutaka
人防御素-5（HD-5）是人小肠潘氏细胞分泌的主要抗菌肽之一。HD-5作为前肽产生并储存在潘氏细胞颗粒中，响应于胆碱能试剂或细菌抗原的刺激而分泌。胰蛋白酶的激活过程发生在肠腔中，以产生成熟的HD-5。本研究评估了proHD-5和成熟HD-5在体外杀菌活性和诱导趋化因子分泌方面的差异。成熟的HD-5对所有细菌菌株均表现出杀菌活性。然而，没有酶切的proHD-5对鼠伤寒沙门氏菌和大肠杆菌的抗菌能力较低，但对金黄色葡萄球菌没有抗菌能力。成熟的HD-5也诱导肠上皮细胞增加白细胞介素-8的蛋白和mRNA水平。此外，将肽应用于葡聚糖硫酸钠诱导的小鼠结肠炎。内源性小鼠防御素在小肠中的表达没有改变，并且额外注射外源性HD-5改善了死亡率（p < 0.05）。这项研究证明了人类防御素激活过程的多功能作用，以及在未来应用中使用抗菌肽治疗炎症性肠病的可能性。版权所有（C）2009 S. Karger AG，巴塞尔
Human defensin-5 (HD-5) is one of the major antimicrobial peptides secreted by Paneth cells in the human small intestine. HD-5 is produced and stored as a propeptide in Paneth cell granules, secreted in response to stimulation by cholinergic reagents or bacterial antigens. The activation process by trypsin occurs in the intestinal lumen to produce mature HD-5. This study evaluated the difference between proHD-5 and mature HD-5 in bactericidal activity and induction of chemokine secretion in vitro. Mature HD-5 showed bactericidal activities against all bacterial strains. Though, proHD-5 without enzymatic cleavage possessed less antimicrobial ability against Salmonella typhimurium and Escherichia Coli but not against Staphylococcus aureus. Mature HD-5 also induced intestinal epithelial cells to increase the protein and mRNA levels of interleukin-8. Furthermore, the peptides were applied to dextran sulfate sodium-induced mouse colitis. The expression of endogenous mouse defensins was not changed in the small intestine, and the additional injection of exogenous HD-5 improved mortality (p < 0.05). This study demonstrated the multifunctional roles of the activation process in human defensin and the possibility of using antimicrobial peptides for the treatment of inflammatory bowel diseases in future applications. Copyright (C) 2009 S. Karger AG, Basel