title: Novel anti-inflammatory agent 3-[(dodecylthiocarbonyl)-methyl]-glutarimide ameliorates murine models of inflammatory bowel disease.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Nobuki
authors.initials: N
authors.lastname: Ichikawa
authors.affiliation: Department of Transplant Surgery, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan. kenchan@med.hokudai.ac.jp.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Funakoshi
authors.affiliation: Department of Surgical Pathology, Sapporo-Kosei General Hospital, N-3, E-8-5, Chuo-ku, Sapporo, 060-0033, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Ichihara
authors.affiliation: Department of Transplant Surgery, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Moto
authors.initials: M
authors.lastname: Fukai
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Ogura
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Zaitsu
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Shibasaki
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Koshizuka
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tsunetoshi
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Einama
authors.affiliation: Faculty of Health Sciences, School of Medicine, Hokkaido University, N-12, W-5, Kita-ku, Sapporo, 060-0812, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ozaki
authors.affiliation: Department of Molecular Target Medicine, Aichi Medical University, Yazakokarimata 1-1, Nagakute, 480-1195, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan. s-todo@st-mary-med.or.jp.|Department of Transplant Surgery, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan. s-todo@st-mary-med.or.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Todo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000276:immunology; D010881:Piperidones / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
chemical_list: C573776:3-((dodecylthiocarbonyl)methyl)glutarimide; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D010881:Piperidones; D012333:RNA, Messenger; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D009195:Peroxidase
keywords: 3-[(Dodecylthiocarbonyl)-methyl]-glutarimide; Colitis; Dextran sulfate sodium; Inflammatory bowel disease; Macrophage; Trinitrobenzenesulfonic acid