title: Inhibition of endotoxin-induced uveitis and potentiation of cyclooxygenase-2 protein expression by alpha-melanocyte-stimulating hormone.
abstract: OBJECTIVE
  The efficacy of alpha-melanocyte-stimulating hormone (alpha-MSH) on endotoxin-induced uveitis (EIU) was investigated in rats. Several studies have demonstrated that there are various inflammatory reactions mediated by an alpha-MSH receptor in macrophages. In addition, as it is known that cyclooxygenase (COX)-2 is induced by a variety of stimuli and plays an important role in inflammation, COX-2 expression was also investigated in macrophage cells treated with alpha-MSH in vitro to clarify its anti-inflammatory effect.
  
  
  METHODS
  EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). The number of infiltrating cells and protein concentration in the aqueous humor collected 24 hours after the LPS treatment was determined. The levels of prostaglandin (PG)-E2, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 production were determined. RAW 264.7 cells were pretreated with various concentrations of alpha-MSH for 24 hours and subsequently incubated with 10 microg/mL LPS for 24 hours. COX-2 protein expression was analyzed by Western blot analysis.
  
  
  RESULTS
  alpha-MSH suppressed the development of EIU in a dose-dependent fashion. The treatment with alpha-MSH reduced the PGE2, TNF-alpha, IL-6, and MCP-1 concentrations in aqueous humor. The COX-2 protein expression in the alpha-MSH group decreased.
  
  
  CONCLUSIONS
  This study suggests that alpha-MSH has an antiocular inflammatory effect, by suppression of PGE2, TNF-alpha, IL-6, and MCP-1 production and blocking of COX-2 expression.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, Sapporo, Japan. shiraken@med.hokudai.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Shiratori
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ohgami
authors.forename: Iliyana Bozhidarova
authors.initials: IB
authors.lastname: Ilieva
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Koyama
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yoshida
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015850:Interleukin-6 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D012486:Salmonella typhimurium; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D000521:alpha-MSH / Q000627:therapeutic use*
chemical_list: D018932:Chemokine CCL2; D015850:Interleukin-6; D007527:Isoenzymes; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone