title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4952, USA.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Meisch
authors.forename: Michiko
authors.initials: M
authors.lastname: Nishimura
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Vogel
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Sung
authors.forename: Beth A
authors.initials: BA
authors.lastname: Bednarchik
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Ghosh
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.forename: Thomas
authors.initials: T
authors.lastname: McCormick
authors.forename: Aaron
authors.initials: A
authors.lastname: Weinberg
authors.forename: Alan D
authors.initials: AD
authors.lastname: Levine
mesh_terms: D015153:Blotting, Western; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006801:Humans; D007079:Ileitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D019879:Paneth Cells / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
chemical_list: C422950:DEFB103A protein, human; D010446:Peptide Fragments; D012333:RNA, Messenger; D023083:beta-Defensins