title: Innate mechanisms for Bifidobacterium lactis to activate transient pro-inflammatory host responses in intestinal epithelial cells after the colonization of germ-free rats.
abstract: Bifidobacteria comprise a dominant microbial population group in the human intestinal tract with purported beneficial health effects on the host. In this study, we characterized the molecular mechanisms for the initial interaction of probiotic Bifidobacterium lactis strain BB12 with native and intestinal epithelial cell (IEC) lines. We showed that B. lactis-monoassociated Fisher F344 rats transiently induce phosphorylation/activation of the NF-kappaB transcriptionally active subunit RelA and the mitogen-activated protein kinase (MAPK) p38 in native IEC at day 5 after initial bacterial colonization. In addition, Interleukin 6 (IL-6) gene expression was significantly increased at day 5, demonstrating the physiological relevance of transient transcription factor activation in IEC. In contrast, Bacteroides vulgatus-monoassociated Fisher rats revealed RelA but not p38 MAPK phosphorylation and failed to trigger significant IL-6 gene expression in native IEC. Moreover, we demonstrated that B. lactis triggers NF-kappaB RelA and p38 MAPK phosphorylation in IEC lines. Adenoviral delivery of mutant IKK-beta (Ad5dnIKKbeta) and inhibition of the p38 MAPK pathway through the pharmacological inhibitor SB203580 significantly blocked B. lactis-induced IL-6 gene expression in IEC, suggesting that B. lactis triggers NF-kappaB and MAPK signaling to induce gene expression in the intestinal epithelium. Regarding the mechanisms of bacteria epithelial cell cross-talk, B. lactis-induced IL-6 gene expression was completely inhibited in TLR2 deficient mouse embryogenic fibroblasts (MEF TLR2-/-) as well as TLR2DeltaTIR transfected Mode-K cells. In conclusion, we demonstrated that probiotic bacteria transiently trigger innate signal transduction and pro-inflammatory gene expression in the intestinal epithelium at early stages of bacterial colonization.
authors: Centre for Nutrition and Food Research, Immunobiology of Nutrition, Technical University of Munich, Freising-Weihenstephan, Germany.
authors: Pedro A
authors: PA
authors: Ruiz
authors: Micha
authors: M
authors: Hoffmann
authors: Silke
authors: S
authors: Szcesny
authors: Michael
authors: M
authors: Blaut
authors: Dirk
authors: D
authors: Haller
mesh_terms: D000818:Animals; D001644:Bifidobacterium / Q000276:immunology*; D002460:Cell Line; D003546:Cysteine Endopeptidases; D004791:Enzyme Inhibitors / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D007093:Imidazoles / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007422:Intestines / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D009687:Nuclear Proteins; D010766:Phosphorylation; D019936:Probiotics; D011506:Proteins / Q000276:immunology; D011725:Pyridines / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D051996:Transcription Factor RelA; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D011506:Proteins; D011725:Pyridines; D011956:Receptors, Cell Surface; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D051996:Transcription Factor RelA; D048051:p38 Mitogen-Activated Protein Kinases; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse; C093642:SB 203580