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: Shin Kashima, Mikihiro Fujiya, Hiroaki Konishi, Nobuhiro Ueno, Yuhei Inaba, Kentaro Moriichi, Hiroki Tanabe, Katsuya Ikuta, Takaaki Ohtake, Yutaka Kohgo
• Journal: Translational research : the journal of laboratory and clinical medicine (Transl Res) Vol. 166 Issue 2 Pg. 163-75 (Aug 2015) ISSN: 1878-1810 [Electronic] United States
• PMID: 25766132 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Inflammation Mediators
• Polyphosphates
• Transforming Growth Factor beta1
• Connective Tissue Growth Factor
• Trinitrobenzenesulfonic Acid
• Collagen
• Dextran Sulfate

Topics

• Animals
• Caco-2 Cells
• Chronic Disease
• Colitis (chemically induced, drug therapy, pathology)
• Collagen (metabolism)
• Colon (drug effects, pathology)
• Connective Tissue Growth Factor (metabolism)
• Cytokines (metabolism)
• Dextran Sulfate
• Epithelial Cells (drug effects, metabolism, pathology)
• Fibrosis
• Humans
• Inflammation (pathology)
• Inflammation Mediators (metabolism)
• Levilactobacillus brevis (chemistry)
• Macrophages (drug effects, metabolism, pathology)
• Mice, Inbred C57BL
• Polyphosphates (pharmacology, therapeutic use)
• Probiotics (pharmacology, therapeutic use)
• Transforming Growth Factor beta1 (metabolism)
• Trinitrobenzenesulfonic Acid
• Up-Regulation (drug effects)