Structure-dependent functional properties of human defensin 5

Edited by Masayuki Miyasaka

Received 3 November 2006; received in revised form 6 December 2006; accepted 15 December 2006. published online 03 January 2007.

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.

Abbreviations: HD, human defensin, HNP, human neutrophil peptide, IL, interleukin, TNF, tumor necrosis factor

Keywords: Human defensin 5, Intestinal epithelium, Interleukin 8, TNF-α

a Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD 21201, USA

b Medical Biotechnology Center, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD 21201, USA

c Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA

Corresponding author. Fax: +1 410 706 7583.

PII: S0014-5793(06)01492-X

doi:10.1016/j.febslet.2006.12.036

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