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: M Zilbauer, A Jenke, G Wenzel, D Goedde, J Postberg, A D Phillips, M Lucas, G Noble-Jamieson, F Torrente, C Salvestrini, R Heuschkel, S Wirth
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 17 Issue 10 Pg. 2076-86 (Oct 2011) ISSN: 1536-4844 [Electronic] England
• PMID: 21910169 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

Chemical References

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• DEFA5 protein, human
• DEFA6 protein, human
• Interleukin-8
• Microfilament Proteins
• RNA, Messenger
• TCF4 protein, human
• Transcription Factor 4
• Transcription Factors
• alpha-Defensins
• villin

Topics

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (genetics, metabolism)
• Case-Control Studies
• Child
• Colitis, Ulcerative (genetics, metabolism, pathology)
• Colon (metabolism)
• Crohn Disease (genetics, metabolism, pathology)
• Female
• Fluorescent Antibody Technique
• Humans
• Ileum (metabolism)
• Immunoenzyme Techniques
• Interleukin-8 (genetics, metabolism)
• Intestinal Mucosa (metabolism, pathology)
• Male
• Microfilament Proteins (genetics, metabolism)
• Paneth Cells (metabolism)
• Prognosis
• Prospective Studies
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription Factor 4
• Transcription Factors (genetics, metabolism)
• alpha-Defensins (genetics, metabolism)