Selective downregulation of retinoic acid-inducible gene I within the intestinal epithelial compartment in Crohn's disease

Inflamm Bowel Dis. 2011 Sep;17(9):1943-54. doi: 10.1002/ibd.21572. Epub 2011 Jan 6.

Abstract

Background: A defective innate immune response may contribute to the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Employing a global gene expression analysis, this study was aimed at identifying specifically regulated genes within the epithelial compartment in inflammatory bowel disease (IBD).

Methods: The epithelial fraction of human ileal mucosa samples from surgical specimens was obtained by laser microdissection. Gene expression was examined by global expression profiling (n = 18, Affymetrix), quantitative reverse-transcription polymerase chain reaction (RT-PCR) (n = 35), immunoblot analysis (n = 9), and immunohistochemistry (n = 25).

Results: Global expression profiling revealed a pronounced downregulation of the retinoic acid-inducible gene I (RIG-I) within the epithelial layer of the ileum in patients with CD but not with UC. The downregulation of RIG-I was confirmed by quantitative RT-PCR, immunoblot analysis, and immunohistochemistry.

Conclusions: Epithelial downregulation of RIG-I, a known pattern recognition receptor for viral components, might contribute to alterations of the innate mucosal immune response, particularly in CD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / analysis*
  • Biomarkers / metabolism
  • Blotting, Western
  • Case-Control Studies
  • Cohort Studies
  • Colitis, Ulcerative / genetics*
  • Colitis, Ulcerative / metabolism
  • Crohn Disease / genetics*
  • Crohn Disease / metabolism
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / metabolism
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunoenzyme Techniques
  • Intestinal Mucosa / metabolism*
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers
  • RNA, Messenger
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases