Sulforaphane suppresses vascular adhesion molecule-1 expression in TNF-α-stimulated mouse vascular smooth muscle cells: Involvement of the MAPK, NF-κB and AP-1 signaling pathways

Atherosclerosis is a long-term inflammatory disease of the arterial wall. Increased expression of the cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) is associated with increased proliferation of vascular smooth muscle cells (VSMCs), leading to increased neointima or atherosclerotic lesion formation. Therefore, the functional inhibition of adhesion molecules could be a critical therapeutic target of inflammatory disease. In the present study, we investigate the effect of sulforaphane on the expression of VCAM-1 induced by TNF-alpha in cultured mouse vascular smooth muscle cell lines. Pretreatment of VSMCs for 2 h with sulforaphane (1-5 mu g/ml) dose-dependently inhibited TNF-alpha-induced adhesion of THP-1 monocytic cells and protein expression of VCAM-1. Sulforaphane also suppressed TNF-alpha-induced production of intracellular reactive oxygen species (ROS) and activation of p38, ERK and JNK. Furthermore, sulforaphane inhibited NK-kappa B and AP-1 activation induced by TNF-alpha. Sulforaphane inhibited TNF-alpha-induced I kappa B kinase activation, subsequent degradation of I kappa B alpha and nuclear translocation of p65 NF-kappa B and decreased c-Jun and c-Fos protein level. This study suggests that sulforaphane inhibits the adhesive capacity of VSMC and downregulates the TNF-alpha-mediated induction of VCAM-1 in VSMC by inhibiting the MAPK, NF-kappa B and AP-1 signaling pathways and intracellular ROS production. Thus, sulforaphane may have beneficial effects to suppress inflammation within the atherosclerotic lesion. (C) 2011 Elsevier Inc. All rights reserved.