Anti-inflammatory effect of Lactobacillus casei on Shigella-infected human intestinal epithelial cells

J Immunol. 2006 Jan 15;176(2):1228-37. doi: 10.4049/jimmunol.176.2.1228.

Abstract

Shigella invades the human intestinal mucosa, thus causing bacillary dysentery, an acute recto-colitis responsible for lethal complications, mostly in infants and toddlers. Conversely, commensal bacteria live in a mutualistic relationship with the intestinal mucosa that is characterized by homeostatic control of innate responses, thereby contributing to tolerance to the flora. Cross-talk established between commensals and the intestinal epithelium mediate this active process, the mechanisms of which remain largely uncharacterized. Probiotics such as Lactobacillus casei belong to a subclass of these commensals that modulate mucosal innate responses and possibly display anti-inflammatory properties. We analyzed whether L. casei could attenuate the pro-inflammatory signaling induced by Shigella flexneri after invasion of the epithelial lining. Cultured epithelial cells were infected with L. casei, followed by a challenge with S. flexneri. Using macroarray DNA chips, we observed that L. casei down-regulated the transcription of a number of genes encoding pro-inflammatory effectors such as cytokines and chemokines and adherence molecules induced by invasive S. flexneri. This resulted in an anti-inflammatory effect that appeared mediated by the inhibition of the NF-kappaB pathway, particularly through stabilization of I-kappaBalpha. In a time-course experiment using GeneChip hybridization analysis, the expression of many genes involved in ubiquitination and proteasome processes were modulated during L. casei treatment. Thus, L. casei has developed a sophisticated means to maintain intestinal homeostasis through a process that involves manipulation of the ubiquitin/proteasome pathway upstream of I-kappaBalpha.

MeSH terms

  • Apoptosis / genetics
  • Base Sequence
  • Caco-2 Cells
  • Cell Cycle / genetics
  • Cell Hypoxia / genetics
  • Cell Line
  • DNA / genetics
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Gene Expression Profiling
  • Homeostasis
  • Humans
  • Immunity, Mucosal
  • Inflammation / prevention & control*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology*
  • Lactobacillus casei / immunology*
  • NF-kappa B / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Probiotics*
  • Proteasome Endopeptidase Complex / metabolism
  • Shigella flexneri / pathogenicity*
  • Signal Transduction
  • Ubiquitin / metabolism

Substances

  • NF-kappa B
  • Ubiquitin
  • DNA
  • Proteasome Endopeptidase Complex