Induction of cytokine formation by human intestinal bacteria in gut epithelial cell lines

J Appl Microbiol. 2011 Jan;110(1):353-63. doi: 10.1111/j.1365-2672.2010.04889.x. Epub 2010 Nov 10.

Abstract

Aims: To investigate the effects of human gut micro-organisms on cytokine production by human intestinal cell lines.

Methods and results: Quantitative real-time PCR assays were developed to measure the production of pro-inflammatory (IL-1α, IL-6, IL-18 and TNFα) and anti-inflammatory (TGF-β1, TGF-β2, TGF-β3, IL-4 and IL-10) cytokines in HT-29 and Caco-2 cell lines. They were co-cultured with a range of mucosal bacteria isolated from ulcerative colitis patients, together with lactobacilli and bifidobacteria obtained from healthy people. HT-29 cells were also co-cultured with Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC), enteropathogenic E. coli and Salmonella typhimurium. The majority of commensal bacteria tested suppressed the expression of anti-inflammatory cytokine mRNA, increased IL-18, reduced IL-1α, and with the exception of nonpathogenic E. coli, reduced TNF-α. All overtly pathogenic species increased both pro-inflammatory and anti-inflammatory cytokine mRNA.

Conclusion: Commensal and pathogenic species induced fundamentally different cytokine responses in human intestinal epithelial cell lines.

Significance and impact of the study: Interactions between commensal bacteria tested in this study and the innate immune system were shown to be anti-inflammatory in nature, in contrast to the pathogenic organisms investigated. These data contribute towards our understanding of how potential probiotic species can be used to suppress the pro-inflammatory response in inflammatory bowel disease.

MeSH terms

  • Bacterial Physiological Phenomena*
  • Bifidobacterium / physiology
  • Caco-2 Cells
  • Campylobacter jejuni / physiology
  • Coculture Techniques
  • Colitis, Ulcerative / microbiology
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Epithelial Cells / immunology
  • Epithelial Cells / microbiology
  • Escherichia coli / physiology
  • HT29 Cells
  • Humans
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology*
  • Lactobacillus / physiology
  • Probiotics
  • Salmonella typhimurium / physiology
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Cytokines
  • Interleukins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha