Resveratrol is a polyphenolic compound in red wine that has anti-oxidant and cardioprotective effects in animal models. Reactive oxygen species (ROS) and monocyte chemotactic protein-1 (MCP-1) play key roles in foam cell formation and atherosclerosis. We studied LPS-mediated foam cell formation and the effect of resveratrol. Resveratrol pretreatment strongly suppressed LPS-induced foam cell formation. To determine if resveratrol affected the expression of genes that control ROS generation in macrophages, NADPH oxidase 1 (Nox1) was measured. Resveratrol treatment of macrophages inhibited LPS-induced Nox1 expression as well as ROS generation, and also suppressed LPS-induced MCP-1 mRNA and protein expression. We investigated the upstream targets of Nox1 and MCP-1 expression and found that Akt-forkhead transcription factors of the O class (FoxO3a) is an important signaling pathway that regulates both genes. These inhibitory effects of resveratrol on Nox1 expression and MCP-1 production may target to the Akt and FoxO3a signaling pathways.
Antioxidants/*pharmacology ; Cells, Cultured ; Chemokine CCL2/genetics/*metabolism ; Enzyme Activation/drug effects ; Foam Cells/*drug effects/physiology ; Forkhead Transcription Factors/metabolism ; Humans ; Lipopolysaccharides/pharmacology ; NADH, NADPH Oxidoreductases/genetics/*metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Messenger/metabolism ; Reactive Oxygen Species/*metabolism ; Signal Transduction ; Stilbenes/*pharmacology