title: Probiotic Lactobacillus-induced improvement in murine chronic inflammatory bowel disease is associated with the down-regulation of pro-inflammatory cytokines in lamina propria mononuclear cells.
abstract: IL-6/STAT-3 signals play key roles in inflammatory bowel disease (IBD). It is known that Lactobacillus casei strain Shirota (LcS) improves inflammatory disorders. This study aimed to elucidate the effect of LcS on murine chronic IBD and to clarify the mechanism. We focused the inhibitory effect of LcS on the production of IL-6 in lipopolysaccharide (LPS)-stimulated large intestinal lamina propria mononuclear cells (LI-LPMC) isolated from mice with chronic colitis and in RAW264.7 cells in vitro. We also determined in vivo the effect of LcS on murine chronic IBD models induced with dextran sodium sulphate and SAMP1/Yit mice. Finally, we examined the cellular determinants of LcS for the down-regulation of IL-6 secretion by LI-LPMC, RAW264.7 cells and peripheral blood mononuclear cells (PBMC) derived from patients with ulcerative colitis (UC). LcS, but not other strains of Lactobacillus, inhibited the production of IL-6 in LPS-stimulated LI-LPMC and RAW264.7 cells, down-regulating the nuclear translocation of NF-kappaB. The LcS-diet-improved murine chronic colitis is associated with the reduction of IL-6 synthesis by LI-LPMC. LcS also improved chronic ileitis in SAMP1/Yit mice. The release of IL-6 in vitro in LPS-stimulated LI-LPMC, RAW 264.7 cells and UC-PBMC was inhibited by a polysaccharide-peptidoglycan complex (PSPG) derived from LcS. This probiotic-induced improvement in murine chronic inflammatory bowel disease is associated with the down-regulation of pro-inflammatory cytokines such as IL-6 and IFN-gamma production in LPMC. Therefore, LcS may be a useful probiotic for the treatment of human inflammatory bowel disease.
authors.affiliation: Yakult Central Institute for Microbiological Research, Tokyo, Japan. satoshi-matsumoto@yakult.co.jp
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Hori
authors.forename: K
authors.initials: K
authors.lastname: Mitsuyama
authors.forename: M
authors.initials: M
authors.lastname: Nagaoka
authors.forename: N
authors.initials: N
authors.lastname: Tomiyasu
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Sata
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007079:Ileitis / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology*; D007780:Lacticaseibacillus casei / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology; D010457:Peptidoglycan / Q000276:immunology; D019936:Probiotics; D011956:Receptors, Cell Surface / Q000276:immunology; D051193:Toll-Like Receptors
chemical_list: D015850:Interleukin-6; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D015847:Interleukin-4; D007371:Interferon-gamma