de Leeuw Erik, Burks Scott R, Li Xiangqun, Kao Joseph P Y, Lu Wuyuan
Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD 21201, USA.
FEBS Lett. 2007 Feb 6;581(3):515-20. doi: 10.1016/j.febslet.2006.12.036. Epub 2007 Jan 2.
The mucosal epithelium secretes a variety of antimicrobial peptides that act as part of the innate immune system to protect against invading microbes. Here, we describe the functional properties of human defensin (HD) 5, the major antimicrobial peptide produced by Paneth cells in the ileum, in relation to its structure. The antimicrobial activity of HD-5 against Escherichia coli proved to be independent of its structure, whereas the unstructured peptide showed greatly reduced antimicrobial activity against Staphylococcus aureus. We find that HD-5 binds to the cell membrane of intestinal epithelial cells and induced secretion of the chemokine interleukin (IL)-8 in a concentration- and structure-dependent fashion. Incubation of HD-5 in the presence of tumor necrosis factor alpha further increased IL-8 secretion synergistically, suggesting that HD-5 may act as a regulator of the intestinal inflammatory response.
黏膜上皮分泌多种抗菌肽,这些抗菌肽作为固有免疫系统的一部分,发挥作用以抵御入侵的微生物。在此,我们描述了人防御素(HD)5的功能特性,HD 5是回肠潘氏细胞产生的主要抗菌肽,同时还涉及到它的结构。HD - 5对大肠杆菌的抗菌活性被证明与其结构无关,而无结构的肽对金黄色葡萄球菌的抗菌活性则大大降低。我们发现HD - 5结合于肠道上皮细胞的细胞膜,并以浓度和结构依赖的方式诱导趋化因子白细胞介素(IL)- 8的分泌。在肿瘤坏死因子α存在的情况下孵育HD - 5可进一步协同增加IL - 8的分泌,这表明HD - 5可能作为肠道炎症反应的调节因子发挥作用。