期刊
INFLAMMATORY BOWEL DISEASES
卷 19, 期 5, 页码 942-953出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MIB.0b013e318280b11a
关键词
beta-defensins; inflammatory bowel disease; Crohn's disease; immunomodulation; epithelium; innate immunity
资金
- National Institute of Health [2R01 DK-54213, 1R21 AI-53188, R01 DE-018276, P01 DE-019759]
- Cytometry & Imaging Microscopy Core Facility of the Case Comprehensive Cancer Center [P30 CA-43703]
- Case Western Reserve University Skin Diseases Research Center [5P30 AR-039750]
- Crohn's and Colitis Foundation of America
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 beta-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.
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