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Title: Osteopontin Deficiency Accelerates Spontaneous Colitis in Mice with Disrupted Gut Microbiota and Macrophage Phagocytic Activity.
Authors: Toyonaga, Takahiko
Nakase, Hiroshi
Ueno, Satoru
Matsuura, Minoru  kyouindb  KAKEN_id
Yoshino, Takuya
Honzawa, Yusuke  kyouindb  KAKEN_id
Itou, Ayako
Namba, Kazuyoshi
Minami, Naoki
Yamada, Satoshi
Koshikawa, Yorimitsu
Uede, Toshimitsu
Chiba, Tsutomu
Okazaki, Kazuichi
Author's alias: 豊永, 貴彦
仲瀬, 裕志
Issue Date: 14-Aug-2015
Publisher: Public Library of Science
Journal title: PLOS ONE
Volume: 10
Issue: 8
Thesis number: e0135552
Abstract: [Background]Osteopontin (OPN) is a multifunctional protein expressed in a variety of tissues and cells. Recent studies revealed increased OPN expression in the inflamed intestinal tissues of patients with inflammatory bowel disease (IBD). The role of OPN in the pathophysiology of IBD, however, remains unclear. [Aims]To investigate the role of OPN in the development of intestinal inflammation using a murine model of IBD, interleukin-10 knock out (IL-10 KO) mice. [Methods]We compared the development of colitis between IL-10 KO and OPN/IL-10 double KO (DKO) mice. OPN expression in the colonic tissues of IL-10 KO mice was examined by fluorescence in situ hybridization (FISH) analysis. Enteric microbiota were compared between IL-10 KO and OPN/IL-10 DKO mice by terminal restriction fragment length polymorphism analysis. The effect of OPN on macrophage phagocytic function was evaluated by phagocytosis assay. [Results]OPN/IL-10 DKO mice had an accelerated onset of colitis compared to IL-10 KO mice. FISH analysis revealed enhanced OPN synthesis in the colonic epithelial cells of IL-10 KO mice. OPN/IL-10 DKO mice had a distinctly different enteric bacterial profile with a significantly lower abundance of Clostridium subcluster XIVa and a greater abundance of Clostridium cluster XVIII compared to IL-10 KO mice. Intracellular OPN deletion in macrophages impaired phagocytosis of fluorescence particle-conjugated Escherichia coli in vitro. Exogenous OPN enhanced phagocytosis by OPN-deleted macrophages when administered at doses of 1 to 100 ng/ml, but not 1000 ng/ml. [Conclusions]OPN deficiency accelerated the spontaneous development of colitis in mice with disrupted gut microbiota and macrophage phagocytic activity.
Rights: © 2015 Toyonaga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
URI: http://hdl.handle.net/2433/202591
DOI(Published Version): 10.1371/journal.pone.0135552
PubMed ID: 26274807
Appears in Collections:Journal Articles

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