Bifidobacterium bifidum reduces apoptosis in the intestinal epithelium in necrotizing enterocolitis
| Autor: | Ludmila Khailova, Kelly M. Arganbright, Melissa D. Halpern, Bohuslav Dvorak, Toshi Kinouchi, Sarah Mount Patrick |
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| Rok vydání: | 2010 |
| Předmět: |
Physiology
Blotting Western ved/biology.organism_classification_rank.species Apoptosis Ileum Biology digestive system Dinoprostone Inflammation/Immunity/Mediators Cell Line Andrology fluids and secretions Bcl-2-associated X protein Intestinal mucosa Enterocolitis Necrotizing Physiology (medical) medicine Animals Intestinal Mucosa Cells Cultured Cell Proliferation bcl-2-Associated X Protein Bifidobacterium Analysis of Variance Chi-Square Distribution Bifidobacterium bifidum Hepatology Caspase 3 Reverse Transcriptase Polymerase Chain Reaction ved/biology Gastroenterology food and beverages Flow Cytometry medicine.disease biology.organism_classification Intestinal epithelium Toll-Like Receptor 2 digestive system diseases Rats medicine.anatomical_structure Cyclooxygenase 2 Necrotizing enterocolitis Immunology biology.protein |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 299:G1118-G1127 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00131.2010 |
| Popis: | Necrotizing enterocolitis (NEC) is a devastating intestinal disease of neonates, and clinical studies suggest the beneficial effect of probiotics in NEC prevention. Recently, we have shown that administration of Bifidobacterium bifidum protects against NEC in a rat model. Intestinal apoptosis can be suppressed by activation of cyclooxygenase-2 (COX-2) and increased production of prostaglandin E2 (PGE2). The present study investigates the effect of B. bifidum on intestinal apoptosis in the rat NEC model and in an intestinal epithelial cell line (IEC-6), as a mechanism of protection against mucosal injury. Premature rats were divided into the following three groups: dam fed, hand fed with formula (NEC), or hand fed with formula supplemented with B. bifidum (NEC + B. bifidum ). Intestinal Toll-like receptor-2 (TLR-2), COX-2, PGE2, and apoptotic regulators were measured. The effect of B. bifidum was verified in IEC-6 cells using a model of cytokine-induced apoptosis. Administration of B. bifidum increased expression of TLR-2, COX-2, and PGE2 and significantly reduced apoptosis in the intestinal epithelium of both in vivo and in vitro models. The Bax-to-Bcl-w ratio was shifted toward cell survival, and the number of cleaved caspase-3 positive cells was markedly decreased in B. bifidum -treated rats. Experiments in IEC-6 cells showed anti-apoptotic effect of B. bifidum . Inhibition of COX-2 signaling blocked the protective effect of B. bifidum treatment in both in vivo and in vitro models. In conclusion, oral administration of B. bifidum activates TLR-2 in the intestinal epithelium. B. bifidum increases expression of COX-2, which leads to higher production of PGE2 in the ileum and protects against intestinal apoptosis associated with NEC. This study indicates the ability of B. bifidum to downregulate apoptosis in the rat NEC model and in IEC-6 cells by a COX-2-dependent matter and suggests a molecular mechanism by which this probiotic reduces mucosal injury and preserves intestinal integrity. |
| Databáze: | OpenAIRE |
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