title: Intestinal alpha-defensin expression in pediatric inflammatory bowel disease.
abstract: BACKGROUND
  Reduced alpha-defensin expression has been reported in the terminal ileum (TI) of adult patients with ileal Crohn's disease (CD). However, little is known about alpha-defensin expression in children with chronic inflammatory bowel disease (IBD).
  
  
  METHODS
  In all, 283 intestinal biopsies were obtained from children with CD, ulcerative colitis (UC), and healthy controls. Absolute mRNA copy numbers for HD5, HD6, IL-8, Villin 1, and Tcf-4 were analyzed by reverse-transcription polymerase chain reaction (RT-PCR). HD5 immunostaining was performed on biopsy sections and patients genotyped for NOD2 mutations.
  
  
  RESULTS
  Equal expression levels of alpha-defensins (HD5 and HD6) were found in TI biopsies of children with ileal CD (L1+L3) compared to patients with colonic disease (L2) and healthy controls. In contrast, we found significantly higher levels of alpha-defensins in the TI of children with UC compared to CD and controls. Reduced expression of Tcf-4 was observed exclusively in the duodenum and TI of CD patients with L1+L3 phenotype. We demonstrate significantly increased expression of HD5 and HD6 in the inflamed colon of IBD children (UC and CD) attributable to the presence of metaplastic Paneth cells.
  
  
  CONCLUSIONS
  In this study no difference in alpha-defensin expression was found in the TI of CD children and controls. However, significant reduction of Tcf-4 in L1+L3 phenotype suggests that a possibly impaired PC differentiation may lead to altered HD5 and HD6 expression at some stage of disease. Additionally, substantially increased expression of alpha-defensins in the inflamed colonic mucosa of children with IBD raises the question for their potential involvement in modulating inflammation in these patients.
authors: Department of Paediatrics, HELIOS Klinikum Wuppertal, Germany. mz304@medschl.cam.ac.uk
authors: M
authors: M
authors: Zilbauer
authors: A
authors: A
authors: Jenke
authors: G
authors: G
authors: Wenzel
authors: D
authors: D
authors: Goedde
authors: J
authors: J
authors: Postberg
authors: A D
authors: AD
authors: Phillips
authors: M
authors: M
authors: Lucas
authors: G
authors: G
authors: Noble-Jamieson
authors: F
authors: F
authors: Torrente
authors: C
authors: C
authors: Salvestrini
authors: R
authors: R
authors: Heuschkel
authors: S
authors: S
authors: Wirth
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007124:Immunoenzyme Techniques; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D019879:Paneth Cells / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D023084:alpha-Defensins / Q000235:genetics* / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C500225:DEFA5 protein, human; C517765:DEFA6 protein, human; D016209:Interleukin-8; D008840:Microfilament Proteins; D012333:RNA, Messenger; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D023084:alpha-Defensins; C026615:villin