title: A component of polysaccharide peptidoglycan complex on Lactobacillus induced an improvement of murine model of inflammatory bowel disease and colitis-associated cancer.
abstract: Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signals play key roles in the pathogenesis of inflammatory bowel disease (IBD). We previously described that both intact cells and a cell wall-derived polysaccharide-peptidoglycan complex (PSPG) in a strain of lactobacillus [Lactobacillus casei Shirota (LcS)] inhibited IL-6 production in lipopolysaccharide (LPS)-stimulated lamina propria mononuclear cells (LPMCs) isolated from murine IBD. Diets with LcS improve murine IBD by suppression of IL-6 synthesis in LPMCs. Moreover, LcS supplementation with fermented milk ameliorates disease activity in patients with active ulcerative colitis. Here, we focused on the specific roles of PSPG in LcS concerning their anti-inflammatory actions. PSPG derived from LcS, and no other strain of lactobacilli, inhibited IL-6 production in LPS-stimulated murine IBD LPMCs. Purified PSPG-I from LcS inhibited IL-6 synthesis in LPS-stimulated murine IBD LPMCs through the inhibition of nuclear factor-kappaB. The anti-IL-6 action of LcS PSPG was abrogated by masking with monoclonal anti-PSPG-I. Furthermore, PSPG-I-negative L. casei strains (PSPG-I-negative mutant LcS: LC(DeltaPSPG-I), L. casei ATCC 334) did not inhibit IL-6 production. Finally, we confirmed the effects of PSPG-I on LcS in the models of both IBD and colitis-associated cancer (CAC). In the IBD model, ingestion of LcS improved ileitis and inhibited activation of IL-6/STAT3 signaling, while ingestion of the LC(DeltaPSPG-I) strain did not. In the CAC model, treatment with LcS, but not the LC(DeltaPSPG-I) strain, showed tumour-suppressive effects with an inhibition of IL-6 production in the colonic mucosa. These results suggested that a specific polysaccharide component in an L. casei strain plays a crucial role in its anti-inflammatory actions in chronic intestinal inflammatory disorders.
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: M
authors.initials: M
authors.lastname: Nagaoka
authors.forename: A
authors.initials: A
authors.lastname: Mike
authors.forename: K
authors.initials: K
authors.lastname: Mitsuyama
authors.forename: T
authors.initials: T
authors.lastname: Sako
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Kado
authors.forename: T
authors.initials: T
authors.lastname: Takada
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002908:Chronic Disease; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000628:therapy*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007780:Lacticaseibacillus casei / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000209:etiology / Q000628:therapy*; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology / Q000378:metabolism; D010457:Peptidoglycan / Q000276:immunology / Q000627:therapeutic use*; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000627:therapeutic use*; D019936:Probiotics / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D000097782:NF-kappaB-Inducing Kinase; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D016264:Dextran Sulfate; D007155:Immunologic Factors; D015850:Interleukin-6; D053473:Nod2 Signaling Adaptor Protein; D010457:Peptidoglycan; D011135:Polysaccharides, Bacterial; D017346:Protein Serine-Threonine Kinases; D050796:STAT3 Transcription Factor; D000097782:NF-kappaB-Inducing Kinase; D000093242:Interleukin-6 Inhibitors; C495945:Nod2 protein, mouse; C494087:Stat3 protein, mouse