Inflammatory Bowel Diseases

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Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e318280b11a
Original Basic Science Articles

Human β-Defensin 3 Peptide Is Increased and Redistributed in Crohn’s Ileitis

Meisch, Jeffrey P. MS*; Nishimura, Michiko DDS†,‡; Vogel, Ryan M. BS*; Sung, Hannah C. BA*; Bednarchik, Beth A. RN*; Ghosh, Santosh K. PhD; Fu, Pingfu PhD§; McCormick, Thomas PhD; Weinberg, Aaron DDM, PhD; Levine, Alan D. PhD*,‡,¶,**,††

Supplemental Author Material
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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.

© Crohn's & Colitis Foundation of America, Inc.

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