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A component of polysaccharide peptidoglycan complex on Lactobacillus induced an improvement of murine model of inflammatory bowel disease and colitis‐associated cancer
Author(s) -
Matsumoto S.,
Hara T.,
Nagaoka M.,
Mike A.,
Mitsuyama K.,
Sako T.,
Yamamoto M.,
Kado S.,
Takada T.
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02942.x
Subject(s) - lactobacillus casei , muramyl dipeptide , inflammatory bowel disease , colitis , peptidoglycan , microbiology and biotechnology , lipopolysaccharide , biology , immunology , medicine , biochemistry , immune system , disease , fermentation , enzyme
Summary 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‐κB. 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 ΔPSPG‐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 ΔPSPG‐I strain did not. In the CAC model, treatment with LcS, but not the LC ΔPSPG‐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.