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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.

journal_name

Inflamm Bowel Dis

journal_title

Inflammatory bowel diseases

authors

Meisch JP,Nishimura M,Vogel RM,Sung HC,Bednarchik BA,Ghosh SK,Fu P,McCormick T,Weinberg A,Levine AD

doi

10.1097/MIB.0b013e318280b11a

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

942-53

issue

eissn

1078-0998

issn

1536-4844

journal_volume

pub_type

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