Systematic name M8916
Brief description Genes down-regulated in Caco-2 cells (intestinal epithelium) after coculture with the probiotic bacteria L. casei for 2h.
Full description or 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16394013   Authors: Tien MT,Girardin SE,Regnault B,Bourhis Le L,Dillies MA,Coppée JY,Bourdet-Sicard R,Sansonetti PJ,Pédron T
Exact source Table 1S: 2h coculture
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform AFFY_HG_U133
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Version history 3.0: First introduced

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