title: Sulforaphane inhibits TNF-alpha-induced activation of p38 MAP kinase and VCAM-1 and MCP-1 expression in endothelial cells.
abstract: OBJECTIVE
  To investigate the effects of sulforaphane on endothelial inflammatory gene expression in endothelial cells.
  
  
  METHODS
  Human aortic endothelial cells were used in the study.
  
  
  RESULTS
  One-hour pretreatment of endothelial cells (EC) with sulforaphane (1-4 muM) suppressed TNF-alpha-induced MCP-1 and VCAM-1 mRNA and protein levels, but had no effect on TNF-alpha-induced ICAM-1 expression. Sulforaphane also inhibited TNF-alpha-induced activation of p38 MAP kinase, but not c-Jun-N-terminal kinase. Sulforaphane had no effect on TNF-alpha-induced NF-kappaB nuclear binding activity, IkappaB-alpha degradation or activation of NF-kappaB-driven transcriptional activity. Expression of dominant negative Nrf2 inhibited sulforaphane-induced antioxidant response element (ARE)-driven promoter activity, but had no effect on sulforaphane-mediated inhibition of VCAM-1 and MCP-1 expression.
  
  
  CONCLUSIONS
  These data suggest that sulforaphane may be useful as a therapeutic agent for the treatment of inflammatory diseases.
authors.affiliation: Discovery Research, AtheroGenics, Inc., 8995 Westside Parkway, Alpharetta, GA 30004, USA. xchen@atherogenics.com
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Chen
authors.forename: Geraldine
authors.initials: G
authors.lastname: Dodd
authors.forename: Charles
authors.initials: C
authors.lastname: Kunsch
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D001324:Autoantigens / Q000096:biosynthesis*; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017879:Isothiocyanates; D009000:Monocytes / Q000502:physiology; D051267:NF-E2-Related Factor 2 / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D001324:Autoantigens; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D012333:RNA, Messenger; D013454:Sulfoxides; D013861:Thiocyanates; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C487774:metaphase chromosome protein 1, human; D004247:DNA; D048051:p38 Mitogen-Activated Protein Kinases; C016766:sulforaphane