論文 - 詳細
| RRC ID | 67905 |
|---|---|
| 著者 | Higashimura Y, Naito Y, Takagi T, Mizushima K, Hirai Y, Harusato A, Ohnogi H, Yamaji R, Inui H, Nakano Y, Yoshikawa T. |
| タイトル | Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression. |
| ジャーナル | J Gastroenterol |
| Abstract |
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. |
| 巻・号 | 48(8) |
| ページ | 897-909 |
| 公開日 | 2013-8-1 |
| DOI | 10.1007/s00535-012-0719-4 |
| PMID | 23188093 |
| MeSH | Animals Anti-Inflammatory Agents / administration & dosage Anti-Inflammatory Agents / chemistry Anti-Inflammatory Agents / pharmacology Blotting, Western Cell Line Colitis / physiopathology Colitis / prevention & control* Disease Models, Animal Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Heme Oxygenase-1 / genetics Heme Oxygenase-1 / metabolism* Inflammation / physiopathology Inflammation / prevention & control* Macrophages / drug effects Macrophages / metabolism Male Mice Mice, Inbred C57BL Oligosaccharides / administration & dosage Oligosaccharides / chemistry Oligosaccharides / pharmacology* Real-Time Polymerase Chain Reaction Sepharose / metabolism Time Factors Trinitrobenzenesulfonic Acid / toxicity |
| IF | 6.132 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |