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Novel anti-inflammatory agent 3-[(dodecylthiocarbonyl)-methyl]-glutarimide ameliorates murine models of inflammatory bowel disease

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/64632

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)

Submitter: 市川 伸樹

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