title: Upregulation of Polymeric Immunoglobulin Receptor Expression by the Heat-Inactivated Potential Probiotic Bifidobacterium bifidum OLB6378 in a Mouse Intestinal Explant Model.
abstract: We determined whether a potential probiotic bacterium, Bifidobacterium bifidum OLB6378 (BB6378), exerts beneficial effects on the mucosal immune system in a mouse intestinal explant model. The addition of heat-inactivated BB6378 to intestinal explants prepared from embryonic day 18 BALB/c mice increased the expression of polymeric immunoglobulin receptor (pIgR) mRNA by two- to fivefold. These effects were observed on ileal and colonic explants but not on jejunal explants, suggesting that the BB6378-induced pIgR upregulation is site-specific within the mouse intestine. The upregulation of pIgR protein expression in colonic explants was also detected after 24 h of culture. The results of DNA microarray analysis of ileal and colonic samples indicated that BB6378 increased the gene expression of interleukin (IL)-1α and IL-1β, and IL-1α content in colonic explants was significantly increased after 20 h of culture with BB6378. We then examined the involvement of endogenously induced IL-1α in pIgR mRNA upregulation by using IL-1α knockout (KO) mice. Contrary to our expectations, pIgR mRNA expression was equally upregulated by BB6378 in colonic explants from BALB/c and IL-1α KO mice. Conversely, we examined the involvement of Toll-like receptors in pIgR mRNA upregulation by using MyD88 KO mice. The upregulation of pIgR was completely suppressed in the explants derived from MyD88 KO mice. Taken together, we conclude that in a mouse intestinal explant model, the heat-inactivated potential probiotic BB6378 increases intestinal pIgR expression in a site-specific manner and that the upregulation of pIgR could be explained by a direct microbial effect on the epithelium via Toll-like receptors.
authors.affiliation: Food Science Research Labs, R&D Division, Meiji Co. Ltd., Kanagawa, JapanDepartment of Applied Biological Chemistry, University of Tokyo, Tokyo, JapanDepartment of Pathology, Nihon University School of Dentistry, Tokyo, JapanCenter for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, JapanResearch Center for Human and Environmental Sciences, Shinshu University, Nagano, JapanCREST, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Food Science Research Labs, R&D Division, Meiji Co. Ltd., Kanagawa, JapanDepartment of Applied Biological Chemistry, University of Tokyo, Tokyo, JapanDepartment of Pathology, Nihon University School of Dentistry, Tokyo, JapanCenter for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, JapanResearch Center for Human and Environmental Sciences, Shinshu University, Nagano, JapanCREST, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Terahara
authors.affiliation: Food Science Research Labs, R&D Division, Meiji Co. Ltd., Kanagawa, JapanDepartment of Applied Biological Chemistry, University of Tokyo, Tokyo, JapanDepartment of Pathology, Nihon University School of Dentistry, Tokyo, JapanCenter for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, JapanResearch Center for Human and Environmental Sciences, Shinshu University, Nagano, JapanCREST, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: Food Science Research Labs, R&D Division, Meiji Co. Ltd., Kanagawa, JapanDepartment of Applied Biological Chemistry, University of Tokyo, Tokyo, JapanDepartment of Pathology, Nihon University School of Dentistry, Tokyo, JapanCenter for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, JapanResearch Center for Human and Environmental Sciences, Shinshu University, Nagano, JapanCREST, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Food Science Research Labs, R&D Division, Meiji Co. Ltd., Kanagawa, JapanDepartment of Applied Biological Chemistry, University of Tokyo, Tokyo, JapanDepartment of Pathology, Nihon University School of Dentistry, Tokyo, JapanCenter for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, JapanResearch Center for Human and Environmental Sciences, Shinshu University, Nagano, JapanCREST, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Asano
authors.affiliation: Food Science Research Labs, R&D Division, Meiji Co. Ltd., Kanagawa, JapanDepartment of Applied Biological Chemistry, University of Tokyo, Tokyo, JapanDepartment of Pathology, Nihon University School of Dentistry, Tokyo, JapanCenter for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, JapanResearch Center for Human and Environmental Sciences, Shinshu University, Nagano, JapanCREST, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kakuta
authors.affiliation: Food Science Research Labs, R&D Division, Meiji Co. Ltd., Kanagawa, JapanDepartment of Applied Biological Chemistry, University of Tokyo, Tokyo, JapanDepartment of Pathology, Nihon University School of Dentistry, Tokyo, JapanCenter for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, JapanResearch Center for Human and Environmental Sciences, Shinshu University, Nagano, JapanCREST, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Food Science Research Labs, R&D Division, Meiji Co. Ltd., Kanagawa, JapanDepartment of Applied Biological Chemistry, University of Tokyo, Tokyo, JapanDepartment of Pathology, Nihon University School of Dentistry, Tokyo, JapanCenter for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, JapanResearch Center for Human and Environmental Sciences, Shinshu University, Nagano, JapanCREST, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Totsuka
mesh_terms: D000818:Animals; D001644:Bifidobacterium / Q000276:immunology*; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004622:Embryo, Mammalian; D006358:Hot Temperature; D007082:Ileum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018928:Immunity, Mucosal / Q000187:drug effects; D053582:Interleukin-1alpha / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D009928:Organ Specificity; D019936:Probiotics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics* / Q000276:immunology; D046509:Tissue Culture Techniques; D015854:Up-Regulation / Q000276:immunology
chemical_list: D053582:Interleukin-1alpha; D053583:Interleukin-1beta; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D019056:Receptors, Polymeric Immunoglobulin