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.
Article first published online 18 March 2013
*Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio;
†Department of Clinical Oral Pathology, School of Dentistry, Health Sciences University of Hokkaido, Ishikari Tohbetsu, Hokkaido, Japan; and
Departments of ‡Biological Sciences,
††Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio.
Reprints: Alan D. Levine, PhD, Department of Medicine, Case Western Reserve University School of Medicine BRB 525, 10900 Euclid Avenue, Cleveland, Ohio, 44106-4952 (e-mail: email@example.com).
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Supported by grants from the National Institute of Health (2R01 DK-54213 and 1R21 AI-53188 to A.D.L.; R01 DE-018276 and P01 DE-019759 to A.W.), the Cytometry & Imaging Microscopy Core Facility of the Case Comprehensive Cancer Center (P30 CA-43703), the Case Western Reserve University Skin Diseases Research Center (pilot funding from 5P30 AR-039750 to J.P.M. and A.D.L.), the Crohn’s and Colitis Foundation of America (to R.M.V.).
The authors have no conflicts of interest to disclose.
Received August 23, 2012
Accepted August 24, 2012