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

• Published in: Vascular pharmacology 2012-03, Vol.56 (3), p.131-141
• Main Authors: Kim, Ji-Yun, Park, Hye-Jin, Um, Sung Hee, Sohn, Eun-Hwa, Kim, Byung-Oh, Moon, Eun-Yi, Rhee, Dong-Kwon, Pyo, Suhkneung
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-inflammatory effect; AP-1; Atherosclerosis - drug therapy; Atherosclerosis - immunology; Atherosclerosis - metabolism; Cardiovascular; Cell Adhesion - drug effects; Cell Line; Gene Expression Regulation - drug effects; Genes, Reporter - drug effects; Isothiocyanates; MAP Kinase Signaling System - drug effects; MAPK; Mice; Molecular Targeted Therapy; Monocytes - drug effects; Monocytes - immunology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - immunology; Muscle, Smooth, Vascular - metabolism; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB; Reactive Oxygen Species - metabolism; Recombinant Proteins - metabolism; RNA, Messenger - metabolism; Sulforaphane; Thiocyanates - pharmacology; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Vascular cell adhesion molecule; Vascular Cell Adhesion Molecule-1 - chemistry; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 1537-1891; 1879-3649
• DOI: 10.1016/j.vph.2011.11.007

Abstract 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-α in cultured mouse vascular smooth muscle cell lines. Pretreatment of VSMCs for 2 h with sulforaphane (1–5 μg/ml) dose-dependently inhibited TNF-α-induced adhesion of THP-1 monocytic cells and protein expression of VCAM-1. Sulforaphane also suppressed TNF-α-induced production of intracellular reactive oxygen species (ROS) and activation of p38, ERK and JNK. Furthermore, sulforaphane inhibited NK-κB and AP-1 activation induced by TNF-α. Sulforaphane inhibited TNF-α-induced ΙκΒ kinase activation, subsequent degradation of ΙκΒα and nuclear translocation of p65 NF-κB and decreased c-Jun and c-Fos protein level. This study suggests that sulforaphane inhibits the adhesive capacity of VSMC and downregulates the TNF-α-mediated induction of VCAM-1 in VSMC by inhibiting the MAPK, NF-κB and AP-1 signaling pathways and intracellular ROS production. Thus, sulforaphane may have beneficial effects to suppress inflammation within the atherosclerotic lesion.