Anti-Inflammatory Effect of Lactobacillus casei on Shigella-Infected Human Intestinal Epithelial Cells

• Published in: Journal of Immunology Vol. 176; no. 2; pp. 1228 - 1237
• Main Authors: Tien, Meng-Tsung, Girardin, Stephen E, Regnault, Beatrice, Le Bourhis, Lionel, Dillies, Marie-Agnes, Coppee, Jean-Yves, Bourdet-Sicard, Raphaelle, Sansonetti, Philippe J, Pedron, Thierry
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.01.2006; Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists
• Subjects: Apoptosis - genetics; Base Sequence; Caco-2 Cells; Cell Cycle - genetics; Cell Hypoxia - genetics; Cell Line; DNA - genetics; domain_sdv.mp.prb; domain_sdv.mp.prb.lac; 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; Lactobacillus casei - immunology; Life Sciences; Microbiology and Parasitology; NF-kappa B - metabolism; Oligonucleotide Array Sequence Analysis; Probiotics; Proteasome Endopeptidase Complex - metabolism; Shigella flexneri; Shigella flexneri - pathogenicity; Signal Transduction; Ubiquitin - metabolism
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.176.2.1228

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.