title: Precursor processing of human defensin-5 is essential to the multiple functions in vitro and in vivo.
abstract: 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.
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Ishikawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanabe
authors.forename: Atsuo
authors.initials: A
authors.lastname: Maemoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ito
authors.forename: Jiro
authors.initials: J
authors.lastname: Watari
authors.forename: Toru
authors.initials: T
authors.lastname: Kono
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Fujiya
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ashida
authors.forename: Tokiyoshi
authors.initials: T
authors.lastname: Ayabe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kohgo
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism; D003092:Colitis / Q000188:drug therapy / Q000276:immunology; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D007421:Intestine, Small / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012486:Salmonella typhimurium / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D023084:alpha-Defensins / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018925:Chemokines; C500225:DEFA5 protein, human; D016209:Interleukin-8; D023084:alpha-Defensins