title: Polyphosphate, an active molecule derived from probiotic Lactobacillus brevis, improves the fibrosis in murine colitis.
abstract: Inflammatory bowel disease frequently causes intestinal obstruction because of extensive fibrosis. This study investigated whether polyphosphate (poly P), an active molecule derived from Lactobacillus brevis, could improve the fibrosis in a model of chronic colitis. In this study, dextran sodium sulfate (DSS)-induced chronic colitis models and trinitrobenzene sulfonic acid (TNBS)-induced colitis models were used as models of fibrosis. To clarify the mechanism responsible for the observed effects, Caco-2/brush border epithelial (BBE) and naive T helper lymphocyte (THP)-1 cells were treated with lipopolysaccharide (LPS) to induce inflammation. Non-cancer human colon fibroblast (CCD-18) cells were treated with transforming growth factor beta 1 (TGF-β1) to induce fibrosis. The expression levels of fibrosis- and inflammation-associated molecules were evaluated by both a Western blotting analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). The histologic inflammation and fibrosis were significantly improved in the group administered poly P in both the DSS and TNBS colitis models. The levels of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were significantly decreased by poly P treatment. The expression levels of TGF-β1 and collagens in the colitis mice were decreased by poly P. The LPS-induced expressions of IL-1β and TGF-β1 in Caco-2/BBE cells and of TNF-α in THP-1 cells were reduced by poly P treatment. Poly P did not affect the expression of collagens and connective tissue growth factor in the CCD-18 cells. In conclusion, poly P suppresses intestinal inflammation and fibrosis by downregulating the expression of inflammation- and fibrosis-associated molecules in the intestinal epithelium. The administration of poly P is therefore a novel option to treat fibrosis because of chronic intestinal inflammation.
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Kashima
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan. Electronic address: fjym@asahikawa-med.ac.jp.
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Fujiya
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Konishi
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ueno
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Inaba
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Moriichi
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanabe
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Ikuta
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ohtake
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kohgo
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D052196:Levilactobacillus brevis / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D011122:Polyphosphates / Q000494:pharmacology / Q000627:therapeutic use*; D019936:Probiotics / Q000494:pharmacology / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D011122:Polyphosphates; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D014302:Trinitrobenzenesulfonic Acid; D003094:Collagen; D016264:Dextran Sulfate