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: Chisato Ishikawa, Hiroki Tanabe, Atsuo Maemoto, Takahiro Ito, Jiro Watari, Toru Kono, Mikihiro Fujiya, Toshifumi Ashida, Tokiyoshi Ayabe, Yutaka Kohgo
• Journal: Journal of innate immunity (J Innate Immun) Vol. 2 Issue 1 Pg. 66-76 ( 2010) ISSN: 1662-8128 [Electronic] Switzerland
• PMID: 20375624 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2009 S. Karger AG, Basel.

Chemical References

• Chemokines
• DEFA5 protein, human
• Interleukin-8
• alpha-Defensins

Topics

• Animals
• Chemokines (metabolism)
• Colitis (drug therapy, immunology)
• Escherichia coli (drug effects)
• Humans
• Interleukin-8 (biosynthesis)
• Intestine, Small (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Salmonella typhimurium (drug effects)
• Staphylococcus aureus (drug effects)
• alpha-Defensins (metabolism, pharmacology, therapeutic use)