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

• Published in: Inflammation research 2009-08, Vol.58 (8), p.513-521
• Main Authors: Chen, Xi-Lin, Dodd, Geraldine, Kunsch, Charles
• Format: Article
• Language: English
• Subjects: Allergology; Anticarcinogenic Agents - pharmacology; Antioxidants - metabolism; Autoantigens - biosynthesis; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cells, Cultured; Dermatology; DNA - genetics; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Enzyme Activation - drug effects; Enzyme-Linked Immunosorbent Assay; Humans; Immunology; Isothiocyanates; Monocytes - physiology; Neurology; NF-E2-Related Factor 2 - physiology; NF-kappa B - metabolism; Original Research Paper; p38 Mitogen-Activated Protein Kinases - metabolism; Pharmacology/Toxicology; Plasmids - genetics; Rheumatology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Signal Transduction - drug effects; Thiocyanates - pharmacology; Transfection; Tumor Necrosis Factor-alpha - pharmacology; U937 Cells; Vascular Cell Adhesion Molecule-1 - biosynthesis
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-009-0017-7

Objective and design To investigate the effects of sulforaphane on endothelial inflammatory gene expression in endothelial cells. Materials and methods Human aortic endothelial cells were used in the study. Results One-hour pretreatment of endothelial cells (EC) with sulforaphane (1–4 μM) suppressed TNF-α-induced MCP-1 and VCAM-1 mRNA and protein levels, but had no effect on TNF-α-induced ICAM-1 expression. Sulforaphane also inhibited TNF-α-induced activation of p38 MAP kinase, but not c-Jun-N-terminal kinase. Sulforaphane had no effect on TNF-α-induced NF-κB nuclear binding activity, IκB-α degradation or activation of NF-κB-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. Conclusion These data suggest that sulforaphane may be useful as a therapeutic agent for the treatment of inflammatory diseases.