PT  - JOURNAL ARTICLE
AU  - Tien, Meng-Tsung
AU  - Girardin, Stephen E.
AU  - Regnault, Béatrice
AU  - Le Bourhis, Lionel
AU  - Dillies, Marie-Agnès
AU  - Coppée, Jean-Yves
AU  - Bourdet-Sicard, Raphaëlle
AU  - Sansonetti, Philippe J.
AU  - Pédron, Thierry
TI  - Anti-Inflammatory Effect of <em>Lactobacillus casei</em> on <em>Shigella</em>-Infected Human Intestinal Epithelial Cells
AID  - 10.4049/jimmunol.176.2.1228
DP  - 2006 Jan 15
TA  - The Journal of Immunology
PG  - 1228--1237
VI  - 176
IP  - 2
4099  - http://www.jimmunol.org/content/176/2/1228.short
4100  - http://www.jimmunol.org/content/176/2/1228.full
SO  - J. Immunol.2006 Jan 15; 176
AB  - 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-κB pathway, particularly through stabilization of I-κBα. 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-κBα.