title: Bifidobacterium breve MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect.
abstract: Bifidobacterium breve MCC-117 is able to significantly reduce the expression of inflammatory cytokines in porcine intestinal epithelial (PIE) cells and to improve IL-10 levels in CD4(+)CD25(high) Foxp3(+) lymphocytes in response to heat-stable enterotoxigenic Escherichia coli (ETEC) pathogen-associated molecular patterns (PAMPs), while the immunoregulatory effect of B. adolescentis ATCC15705 was significantly lower than that observed for the MCC-117 strain. Considering the different capacities of the two bifidobacterium strains to activate toll-like receptor (TLR)-2 and their differential immunoregulatory activities in PIE and immune cells, we hypothesized that comparative studies with both strains could provide important information regarding the molecular mechanism(s) involved in the anti-inflammatory activity of bifidobacteria. In this work, we demonstrated that the anti-inflammatory effect of B. breve MCC-117 was achieved by a complex interaction of multiple negative regulators of TLRs as well as inhibition of multiple signaling pathways. We showed that B. breve MCC-117 reduced heat-stable ETEC PAMP-induced NF-κB, p38 MAPK and PI3 K activation and expression of pro-inflammatory cytokines in PIE cells. In addition, we demonstrated that B. breve MCC-117 may activate TLR2 synergistically and cooperatively with one or more other pattern recognition receptors (PRRs), and that interactions may result in a coordinated sum of signals that induce the upregulation of A20, Bcl-3, Tollip and SIGIRR. Upregulation of these negative regulators could have an important physiological impact on maintaining or reestablishing homeostatic TLR signals in PIE cells. Therefore, in the present study, we gained insight into the molecular mechanisms involved in the immunoregulatory effect of B. breve MCC-117.
authors.affiliation: Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
authors.forename: Kozue
authors.initials: K
authors.lastname: Murata
authors.affiliation: Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Tomosada
authors.affiliation: Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan ; Laboratory of Clinical and Experimental Biochemistry, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina.
authors.forename: Julio
authors.initials: J
authors.lastname: Villena
authors.affiliation: Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Chiba
authors.affiliation: Laboratory of Animal Breeding and Genetics, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shimazu
authors.affiliation: Cell Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Aso
authors.affiliation: Food Science and Technology Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa, 252-8583, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Iwabuchi
authors.affiliation: Food Science and Technology Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa, 252-8583, Japan.
authors.forename: Jin-Zhong
authors.initials: JZ
authors.lastname: Xiao
authors.affiliation: Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Saito
authors.affiliation: Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kitazawa
keywords: Toll-like receptor 2; Toll-like receptors negative regulators; anti-inflammatory activity; bifidobacteria; porcine intestinal epithelial cells