Human β-defensin 3 peptide is increased and redistributed in Crohn's ileitis.

Abstract

BACKGROUND:

Antimicrobial peptides (AMPs) maintain a sterile environment in intestinal crypts, limiting microbial colonization and invasion. Decreased AMP expression is proposed to increase the risk for inflammatory bowel disease. Expression and function of inducible AMPs, human β-defensin 2 and 3 (hBD-2 and hBD-3), remain poorly characterized in healthy and chronically inflamed intestine.

METHODS:

Peptide concentrations of hBD-2 and hBD-3 in serum and intestinal biopsies of subjects with ulcerative colitis and Crohn's disease (CD), and those of healthy subjects were measured by ELISA. Messenger RNA of hBD-2 and hBD-3 was quantified by quantitative PCR in biopsies from the terminal ileum (TI) of patients with CD and healthy controls. Peptide localization of hBD-3 in the TI was visualized by confocal microscopy.

RESULTS:

Immunoreactive hBD-3 peptide is present in the TI and colon in healthy subjects. In the TI of patients with CD, hBD-3, but not hBD-2 peptide, is increased 4-fold, whereas hBD-2 peptide is elevated in the serum. Messenger RNA of hBD-3 in the CD TI remains unchanged and does not correlate with hBD-3 peptide expression. However, hBD-3 is localized to Paneth cell granules and the apical surface of the healthy columnar epithelium. In CD, hBD-3 peptide location switches to the basolateral surface of the columnar epithelium and is diffusely distributed within the lamina propria.

CONCLUSION:

The peptide hBD-3 throughout the healthy gastrointestinal tract suggests a role in maintaining balance between host defenses and commensal microbiota. Increased and relocalized secretion of hBD-3 toward the lamina propria in the CD TI indicates possible local immunomodulation during chronic inflammation, whereas increased serum hBD-2 in CD implicates its systemic antimicrobial and immunomodulatory role.

• Authors: Jeffrey P Meisch, Michiko Nishimura, Ryan M Vogel, Hannah C Sung, Beth A Bednarchik, Santosh K Ghosh, Pingfu Fu, Thomas McCormick, Aaron Weinberg, Alan D Levine
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 19 Issue 5 Pg. 942-53 (Apr 2013) ISSN: 1536-4844 [Electronic] England
• PMID: 23511030 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• DEFB103A protein, human
• Peptide Fragments
• RNA, Messenger
• beta-Defensins

Topics

• Blotting, Western
• Case-Control Studies
• Crohn Disease (genetics, metabolism, pathology)
• Enzyme-Linked Immunosorbent Assay
• Gastrointestinal Tract (metabolism)
• Humans
• Ileitis (genetics, metabolism, pathology)
• Immunoenzyme Techniques
• Inflammation (metabolism, pathology)
• Intestinal Mucosa (metabolism)
• Intestines (pathology)
• Paneth Cells (metabolism)
• Peptide Fragments (genetics, metabolism)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• beta-Defensins (genetics, metabolism)