title: Rebamipide inhibits tumor necrosis factor-α-induced interleukin-8 expression by suppressing the NF-κB signal pathway in human umbilical vein endothelial cells.
abstract: OBJECTIVE
  This study was designed to identify the inhibitory effect of rebamipide on tumor necrosis factor-α (TNF-α)-induced interleukin-8 (IL-8) production and nuclear factor-κB (NF-κB) activation in human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  After stimulation with TNF-α, HUVECs were treated with rebamipide in a dose-dependent manner. The viability of HUVECs was assessed using methylthiazol tetrazolium assay after 24 h incubation with rebamipide. TNF-α-induced IL-8 expression was determined by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (RT-PCR). TNF-α-induced IκB-α phosphorylation and translocation of NF-κB p65 subunit into nucleus in endothelial cells were assessed using immunoblot analysis.
  
  
  RESULTS
  We found that rebamipide decreased the expression of IL-8 in the dose-dependent manner under the treatment with TNF-α 10 ng/ml. TNF-α-induced degradation of IκB-α at 15 min was maximally observed and rebamipide (2 mM) inhibited TNF-α-induced phosphorylation of IκB-α in the cytoplasm of endothelial cells by western blot analysis. Rebamipide also suppressed TNF-α-stimulated NF-κB p65 nuclear translocation.
  
  
  CONCLUSIONS
  Rebamipide suppresses TNF-α-induced IL-8 production through (1) inhibition of IκB-α phosphorylation in the cytoplasm and (2) blockage of NF-κB p65 protein transport into the nucleus. We suggest that the anti-inflammatory effect of rebamipide is related to the down-regulation of IL-8 expression that is important in endothelial inflammation.
authors.affiliation: Department of Internal Medicine, Catholic University of Daegu School of Medicine, 3056-6 Daemyung 4-Dong, Namgu, Daegu, 705-718, South Korea.
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Choe
authors.forename: Ki-Yeun
authors.initials: KY
authors.lastname: Park
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Seong-Kyu
authors.initials: SK
authors.lastname: Kim
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D015363:Quinolones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D016209:Interleukin-8; C000606204:NFKBIA protein, human; D015363:Quinolones; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C052785:rebamipide; D000409:Alanine