title: Effect of Lactobacillus brevis KB290 on the cell-mediated cytotoxic activity of mouse splenocytes: a DNA microarray analysis.
abstract: Lactic acid bacteria confer a variety of health benefits. Here, we investigate the mechanisms by which Lactobacillus brevis KB290 (KB290) enhances cell-mediated cytotoxic activity. Female BALB/c mice aged 9 weeks were fed a diet containing KB290 (3 × 10(9) colony-forming units/g) or starch for 1 d. The resulting cytotoxic activity of splenocytes against YAC-1 cells was measured using flow cytometry and analysed for gene expression using DNA microarray technology. KB290 enhanced the cell-mediated cytotoxic activity of splenocytes. DNA microarray analysis identified 327 up-regulated and 347 down-regulated genes that characterised the KB290 diet group. The up-regulated genes were significantly enriched in Gene Ontology terms related to immunity, and, especially, a positive regulation of T-cell-mediated cytotoxicity existed among these terms. Almost all the genes included in the term encoded major histocompatibility complex (MHC) class I molecules involved in the presentation of antigen to CD8(+) cytotoxic T cells. Marco and Signr1 specific to marginal zone macrophages (MZM), antigen-presenting cells, were also up-regulated. Flow cytometric analysis confirmed that the proportion of MZM was significantly increased by KB290 ingestion. Additionally, the over-represented Kyoto Encyclopedia of Genes and Genomes pathways among the up-regulated genes were those for natural killer (NK) cell-mediated cytotoxicity and antigen processing and presentation. The results for the selected genes associated with NK cells and CD8(+) cytotoxic T cells were confirmed by quantitative RT-PCR. These results suggest that enhanced cytotoxic activity could be caused by the activation of NK cells and/or of CD8(+) cytotoxic T cells stimulated via MHC class I presentation.
authors.affiliation: Nature and Wellness Research Department, Research Institute, Kagome Company Limited, 17 Nishitomiyama, Nasushiobara, Tochigi 329-2762, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fukui
authors.forename: Erika
authors.initials: E
authors.lastname: Sasaki
authors.forename: Nobuo
authors.initials: N
authors.lastname: Fuke
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakai
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishijima
authors.forename: Keiko
authors.initials: K
authors.lastname: Abe
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yajima
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism; D052196:Levilactobacillus brevis / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D008223:Lymphoma / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D015854:Up-Regulation; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C092228:Marco protein, mouse