title: Bifidobacterium breve - HT-29 cell line interaction: modulation of TNF-α induced gene expression.
abstract: To provide insight in the molecular basis for intestinal host-microbe interactions, we determined the genome-wide transcriptional response of human intestinal epithelial cells following exposure to cells of Bifidobacterium breve. To select an appropriate test system reflecting inflammatory conditions, the responsiveness to TNF-α was compared in T84, Caco-2 and HT-29 cells. The highest TNF-α response was observed in HT-29 cells and this cell line was selected for exposure to the B. breve strains M-16V, NR246 and UCC2003. After one hour of bacterial pre-incubation followed by two hours of additional TNF-α stimulation, B. breve M-16V (86%), but to a much lesser extent strains NR246 (50%) or UCC2003 (32%), showed a strain-specific reduction of the HT-29 transcriptional response to the inflammatory treatment. The most important functional groups of genes that were transcriptionally suppressed by the presence of B. breve M-16V, were found to be involved in immune regulation and apoptotic processes. About 54% of the TNF-α induced genes were solely suppressed by the presence of B. breve M-16V. These included apoptosis-related cysteine protease caspase 7 (CASP7), interferon regulatory factor 3 (IRF3), amyloid beta (A4) precursor proteinbinding family A member 1 (APBA1), NADPH oxidase (NOX5), and leukemia inhibitory factor receptor (LIFR). The extracellular IL-8 concentration was determined by an immunological assay but did not change significantly, indicating that B. breve M-16V only partially modulates the TNF-α pathway. In conclusion, this study shows that B. breve strains modulate gene expression in HT-29 cells under inflammatory conditions in a strain-specific way.
authors.affiliation: Microbiology Department, TNO Quality of Life, Utrechtseweg, Zeist, the Netherlands. rjboesten@hotmail.com
authors.forename: R J
authors.initials: RJ
authors.lastname: Boesten
authors.forename: F H J
authors.initials: FH
authors.lastname: Schuren
authors.forename: L E M
authors.initials: LE
authors.lastname: Willemsen
authors.forename: A
authors.initials: A
authors.lastname: Vriesema
authors.forename: J
authors.initials: J
authors.lastname: Knol
authors.forename: W M
authors.initials: WM
authors.lastname: De Vos
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001644:Bifidobacterium / Q000502:physiology*; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics; D004847:Epithelial Cells / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D019073:HT29 Cells / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D007249:Inflammation; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D019936:Probiotics; D012329:RNA, Bacterial / Q000235:genetics; D013045:Species Specificity; D013997:Time Factors; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D012329:RNA, Bacterial; D014409:Tumor Necrosis Factor-alpha