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

Ichikawa, Nobuki; Yamashita, Kenichiro; Funakoshi, Tohru; Ichihara, Shin; Fukai, Moto; Ogura, Masaomi; Kobayashi, Nozomi; Zaitsu, Masaaki; Yoshida, Tadashi; Shibasaki, Susumu; Koshizuka, Yasuyuki; Tsunetoshi, Yusuke; Sato, Masanori; Einama, Takahiro; Ozaki, Michitaka; Umezawa, Kazuo; Suzuki, Tomomi; Todo, Satoru

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

Ichikawa, Nobuki; Yamashita, Kenichiro; Funakoshi, Tohru et al.

Inflammation Research, 2016, 65(3), 245-260

Permalink : https://hdl.handle.net/2115/64632

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アクセス権	open access
URI	https://hdl.handle.net/2115/64632
タイトル	Novel anti-inflammatory agent 3-[(dodecylthiocarbonyl)-methyl]-glutarimide ameliorates murine models of inflammatory bowel disease
著者	Ichikawa, Nobuki ; Yamashita, Kenichiro ; Funakoshi, Tohru ; Ichihara, Shin ; Fukai, Moto ; Ogura, Masaomi ; Kobayashi, Nozomi ; Zaitsu, Masaaki ; Yoshida, Tadashi ; Shibasaki, Susumu ; Koshizuka, Yasuyuki ; Tsunetoshi, Yusuke ; Sato, Masanori ; Einama, Takahiro ; Ozaki, Michitaka ; Umezawa, Kazuo ; Suzuki, Tomomi ; Todo, Satoru
e-Rad_Researcher 50779890 著者名 Ichikawa, Nobuki
e-Rad_Researcher 00399940 著者名 Yamashita, Kenichiro
著者名 Funakoshi, Tohru
著者名 Ichihara, Shin
e-Rad_Researcher 60374344 著者名 Fukai, Moto
著者名 Ogura, Masaomi
著者名 Kobayashi, Nozomi
著者名 Zaitsu, Masaaki
著者名 Yoshida, Tadashi
著者名 Shibasaki, Susumu
著者名 Koshizuka, Yasuyuki
著者名 Tsunetoshi, Yusuke
著者名 Sato, Masanori
著者名 Einama, Takahiro
e-Rad_Researcher 80256510 著者名 Ozaki, Michitaka
e-Rad_Researcher 70114402 著者名 Umezawa, Kazuo
e-Rad_Researcher 70374238 著者名 Suzuki, Tomomi
e-Rad_Researcher 60136463 著者名 Todo, Satoru
言語	英語
キーワード	Inflammatory bowel disease
	3-[(Dodecylthiocarbonyl)-methyl]-glutarimide
	Trinitrobenzenesulfonic acid
	Dextran sulfate sodium
	Colitis
	Macrophage
発行日	2016-03
出版者	Springer
収録物名	Inflammation Research
巻(号)	65(3)
ページ	245-260
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	The final publication is available at link.springer.com
PISSN	1023-3830
関連情報	PMID 26683259
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1007/s00011-015-0911-0