| Title: | Novel anti-inflammatory agent 3-[(dodecylthiocarbonyl)-methyl]-glutarimide ameliorates murine models of inflammatory bowel disease |
| Authors: | Ichikawa, Nobuki Browse this author →KAKEN DB |
| Yamashita, Kenichiro Browse this author →KAKEN DB |
| Funakoshi, Tohru Browse this author |
| Ichihara, Shin Browse this author |
| Fukai, Moto Browse this author →KAKEN DB |
| Ogura, Masaomi Browse this author |
| Kobayashi, Nozomi Browse this author |
| Zaitsu, Masaaki Browse this author |
| Yoshida, Tadashi Browse this author |
| Shibasaki, Susumu Browse this author |
| Koshizuka, Yasuyuki Browse this author |
| Tsunetoshi, Yusuke Browse this author |
| Sato, Masanori Browse this author |
| Einama, Takahiro Browse this author |
| Ozaki, Michitaka Browse this author →KAKEN DB |
| Umezawa, Kazuo Browse this author →KAKEN DB |
| Suzuki, Tomomi Browse this author →KAKEN DB |
| Todo, Satoru Browse this author →KAKEN DB |
| Keywords: | Inflammatory bowel disease |
| 3-[(Dodecylthiocarbonyl)-methyl]-glutarimide |
| Trinitrobenzenesulfonic acid |
| Dextran sulfate sodium |
| Colitis |
| Macrophage |
| Issue Date: | Mar-2016 |
| Publisher: | Springer |
| Journal Title: | Inflammation Research |
| Volume: | 65 |
| Issue: | 3 |
| Start Page: | 245 |
| End Page: | 260 |
| Publisher DOI: | 10.1007/s00011-015-0911-0 |
| PMID: | 26683259 |
| Abstract: | Objective and design: To examine the effect of 3-[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G), a novel anti-inflammatory agent that inhibits lipopolysaccharide (LPS) activation of RAW264.7 macrophages, on murine models of colitis and RAW264.7 cells. Materials and methods: Colitis was induced by rectally infusing trinitrobenzenesulfonic acid (TNBS) (1.5 mg in 50 % ethanol) in BALB/c mice or orally administering 3 % dextran sulfate sodium (DSS) for 5 days in C57BL/6 mice. The severity of colitis was assessed after intraperitoneally injecting DTCM-G (40 mg/kg). The anti-inflammatory properties of DTCM-G and its mechanisms were investigated in LPS-stimulated RAW264.7 cells. Results: DTCM-G significantly ameliorated TNBS-induced colitis, according to the body weight loss, disease activity index, colonic obstruction, macroscopic colonic inflammation score, mucosal myeloperoxidase activity, and histopathology. Immunohistochemistry and isolated lamina propria mononuclear cells showed significantly reduced colonic F4/80+ and CD11b+ macrophage infiltration. DTCM-G significantly suppressed tumor necrosis factor (TNF)-α and interleukin (IL)-6 messenger RNA expression in the colon and attenuated DSS-induced colitis, according to the disease activity index and histopathology. In RAW264.7 cells, DTCM-G suppressed LPS-induced TNF-α/IL-6 production and enhanced glycogen synthase kinase-3β phosphorylation. Conclusions: DTCM-G attenuated murine experimental colitis by inhibiting macrophage infiltration and inflammatory cytokine expression. Thus, DTCM-G may be a promising treatment for inflammatory bowel disease. |
| Rights: | The final publication is available at link.springer.com |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/64632 |
| Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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