Sulforaphane inhibits TNF-α-induced activation of p38 MAP kinase and VCAM-1 and MCP-1 expression in endothelial cells

Abstract

To investigate the effects of sulforaphane on endothelial inflammatory gene expression in endothelial cells. Human aortic endothelial cells were used in the study. 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. These data suggest that sulforaphane may be useful as a therapeutic agent for the treatment of inflammatory diseases.