Sulforaphane inhibits TNF-alpha-induced activation of p38 MAP kinase and VCAM-1 and MCP-1 expression in endothelial cells.
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.
Chen
Xi-Lin
XL
Discovery Research, AtheroGenics, Inc., 8995 Westside Parkway, Alpharetta, GA 30004, USA. xchen@atherogenics.com
Dodd
Geraldine
G
Kunsch
Charles
C
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*
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