title: Impact of adrenomedullin on dextran sulfate sodium-induced inflammatory colitis in mice: insights from in vitro and in vivo experimental studies.
abstract: BACKGROUND
  Although adrenomedullin (AM) is known to ameliorate inflammatory processes, few data exist regarding the effect of AM on inflammatory colitis. Therefore, we examined the effect of AM on inflammatory response in vitro and in vivo colitis model.
  
  
  METHODS
  In mice experimental colitis induced by 3% dextran sulfate sodium (DSS) in drinking water for 7 days, AM with 225-900 μg/kg in 0.5 ml of saline or saline alone were given intraperitoneally once a day. In the in vitro experiment, we determined the cytokine response in THP-1 cell activated by lipopolysaccharide with or without AM of 10 nM. Additionally, we performed wound healing assay in Caco-2 cell interfered by DSS with or without AM of 100 nM.
  
  
  RESULTS
  In the colitis model, AM significantly reduced the disease activity index, histological score, and local production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in accordance with reduction of serum amyloid A levels. Secretion of TNF-α in lipopolysaccharide-stimulated THP-1 cells was significantly reduced in the presence of AM. The distance of wound healing interfered by 0.25% DSS was significantly improved in the presence of AM of 100 nM.
  
  
  CONCLUSIONS
  These results demonstrate that AM could ameliorate DSS-induced experimental colitis possibly through suppression of systemic and local production of cytokines such as TNF-α, associated with acceleration of ulcer reepithelialization and colon tissue regeneration.
authors.affiliation: Department of Internal Medicine, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Kenta
authors.initials: K
authors.lastname: Narumi
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Tsuji
authors.forename: Toshinari
authors.initials: T
authors.lastname: Tsubokawa
authors.forename: Masa-aki
authors.initials: MA
authors.lastname: Nakaya
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Wakayama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Zuka
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohshima
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamagishi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Okada
mesh_terms: D053607:Adrenomedullin / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D016264:Dextran Sulfate; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism; D014456:Ulcer / Q000150:complications / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D000685:Serum Amyloid A Protein; D053607:Adrenomedullin; D016264:Dextran Sulfate; D009195:Peroxidase