Enteropathogenic e.coli sustains iodoacetamide-induced ulcerative colitis-like colitis in rats: modulation of IL-1β, IL-6, TNF-α, COX-2, and apoptosisi

J Biol Regul Homeost Agents. 2012 Jul-Sep;26(3):515-26.

Abstract

Pathogenic or non-pathogenic bacteria from flora may play a key role in inflammatory bowel disease (IBD) pathogenesis. However, a specific infectious agent causing IBD has not been identified. This study assessed the impact of enteropathogenic E. coli (EPEC) on the modulation of IL-1beta, IL-6, TNF- alpha, COX-2, BAX and Bcl-2 expression, in sustaining inflammation of a rat colitis model. Two hundred male Sprague-Dawley rats (4 groups) were inoculated weekly or bi-weekly for 70 days, with 1 percent methylcellulose (MC), (b) 6 percent iodoacetamide (IA) in 1 percent MC, (c) 4x108 CFU of EPEC, and (d) IA+EPEC. After a month, treatment was stopped in half of the animals in each group. IL-1beta, IL-6, TNF-alpha, COX-2, BAX and Bcl-2 expression were measured in colonic mucosa scrapings. IL-1beta, IL-6, TNF-alpha, and COX-2 were significantly increased in colonic mucosa of the IA+EPEC group and to a lesser but significant level in the IA group compared to controls, or EPEC alone, both in continued and discontinued treatment groups. Additionally, the BAX/Bcl-2 ratio decreased, indicating less apoptosis in the IA+EPEC group which exhibited more necrosis. These effects increased with experiment duration. This work provides new arguments favouring the role of bacteria in IBD pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / adverse effects*
  • Alkylating Agents / pharmacology
  • Animals
  • Apoptosis / drug effects*
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / metabolism*
  • Colitis, Ulcerative / microbiology
  • Colitis, Ulcerative / pathology
  • Colon / metabolism
  • Colon / microbiology
  • Colon / pathology
  • Cyclooxygenase 2 / biosynthesis*
  • Enteropathogenic Escherichia coli*
  • Escherichia coli Infections / chemically induced
  • Escherichia coli Infections / metabolism*
  • Escherichia coli Infections / microbiology
  • Escherichia coli Infections / pathology
  • Gene Expression Regulation / drug effects
  • Interleukin-1beta / biosynthesis*
  • Interleukin-6 / biosynthesis*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Iodoacetamide / adverse effects*
  • Iodoacetamide / pharmacology
  • Male
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • bcl-2-Associated X Protein / biosynthesis

Substances

  • Alkylating Agents
  • Bax protein, rat
  • Interleukin-1beta
  • Interleukin-6
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Iodoacetamide