title: Structure-dependent functional properties of human defensin 5.
abstract: 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.
authors.affiliation: Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD 21201, USA. deleeuw@umbi.umd.edu
authors.forename: Erik
authors.initials: E
authors.lastname: de Leeuw
authors.forename: Scott R
authors.initials: SR
authors.lastname: Burks
authors.forename: Xiangqun
authors.initials: X
authors.lastname: Li
authors.forename: Joseph P Y
authors.initials: JP
authors.lastname: Kao
authors.forename: Wuyuan
authors.initials: W
authors.lastname: Lu
mesh_terms: D018938:Caco-2 Cells; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology / Q000502:physiology; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000187:drug effects / Q000382:microbiology / Q000502:physiology; D019879:Paneth Cells / Q000502:physiology; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D023084:alpha-Defensins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000502:physiology*
chemical_list: D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D023084:alpha-Defensins