Precursor Processing of Human Defensin-5 Is Essential to the Multiple Functions in vitro and in vivo

Chisato Ishikawa, Hiroki Tanabe, Atsuo Maemoto, Takahiro Ito, Jiro Watari, Toru Kono, Mikihiro Fujiya, Toshifumi Ashida, Tokiyoshi Ayabe, Yutaka Kohgo
2010 Journal of Innate Immunity  
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. 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
more » ... ide 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
doi:10.1159/000242114 pmid:20375624 fatcat:jqmefhzruzeublf6lmb27tqg5a