| Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression. | |
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MedLine Citation:
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PMID: 23188093 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: Agarose is hydrolyzed easily to yield oligosaccharides, designated as agaro-oligosaccharides (AGOs). Recently, it has been demonstrated that AGOs induce heme oxygenase-1 (HO-1) expression in macrophages and that they might lead to anti-inflammatory property. Nevertheless, the molecular mechanism of AGO-mediated HO-1 induction remains unknown, as does AGOs' ability to elicit anti-inflammatory activity in vivo. This study was undertaken to uncover the mechanism of AGO-mediated HO-1 induction and to investigate the therapeutic effect of AGOs on intestinal inflammation. METHODS: Mice were treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. The respective degrees of mucosal injury of mice that had received AGO and control mice were compared. We investigated HO-1 expression using Western blotting, quantitative real-time PCR (qRT-PCR), and immunohistochemistry. The expression of tumor necrosis factor-α (TNF-α) was measured using qRT-PCR and enzyme-linked immunosorbent assay. RESULTS: AGO administration induced HO-1 expression in colonic mucosa. The induction was observed mainly in F4/80 positive macrophages. Increased colonic damage and myeloperoxidase activity after TNBS treatment were inhibited by AGO administration. TNBS treatment induced TNF-α expression, and AGO administration suppressed induction. However, HO inhibitor canceled AGO-mediated amelioration of colitis. In RAW264 cells, AGOs enhanced HO-1 expression time-dependently and concentration-dependently and suppressed lipopolysaccharide-induced TNF-α expression. Furthermore, agarotetraose-mediated HO-1 induction required NF-E2-related factor 2 function and phosphorylation of c-jun N-terminal kinase. CONCLUSIONS: We infer that AGO administration inhibits TNBS-induced colitis in mice through HO-1 induction in macrophages. Consequently, oral administration of AGOs might be an important therapeutic strategy for inflammatory bowel disease. |
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Authors:
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Yasuki Higashimura; Yuji Naito; Tomohisa Takagi; Katsura Mizushima; Yasuko Hirai; Akihito Harusato; Hiromu Ohnogi; Ryoichi Yamaji; Hiroshi Inui; Yoshihisa Nakano; Toshikazu Yoshikawa |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-28 |
Journal Detail:
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Title: Journal of gastroenterology Volume: - ISSN: 1435-5922 ISO Abbreviation: J. Gastroenterol. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9430794 Medline TA: J Gastroenterol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Kyoto, 602-8566, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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