論文 - 詳細
| RRC ID | 63396 |
|---|---|
| 著者 | Ichikawa N, Yamashita K, Funakoshi T, Ichihara S, Fukai M, Ogura M, Kobayashi N, Zaitsu M, Yoshida T, Shibasaki S, Koshizuka Y, Tsunetoshi Y, Sato M, Einama T, Ozaki M, Umezawa K, Suzuki T, Todo S. |
| タイトル | Novel anti-inflammatory agent 3-[(dodecylthiocarbonyl)-methyl]-glutarimide ameliorates murine models of inflammatory bowel disease. |
| ジャーナル | Inflamm Res |
| 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. |
| 巻・号 | 65(3) |
| ページ | 245-60 |
| 公開日 | 2016-3-1 |
| DOI | 10.1007/s00011-015-0911-0 |
| PII | 10.1007/s00011-015-0911-0 |
| PMID | 26683259 |
| MeSH | Animals Anti-Inflammatory Agents / pharmacology Anti-Inflammatory Agents / therapeutic use* CD4-Positive T-Lymphocytes / drug effects CD4-Positive T-Lymphocytes / immunology Cell Line Colitis / chemically induced Colitis / drug therapy* Colitis / immunology Colitis / pathology Colon / drug effects Colon / immunology Colon / pathology Cytokines / genetics Dextran Sulfate Disease Models, Animal Macrophages / drug effects Macrophages / immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Peroxidase / immunology Piperidones / pharmacology Piperidones / therapeutic use* RNA, Messenger / metabolism Trinitrobenzenesulfonic Acid |
| IF | 3.174 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |