Suppressive effect of quercetin, a bioflavonoid, on TNF-α-mediated stimulation of chemokine expression in cultured human synovial cells

Abstract

Tumor necrosis factor (TNF) -α is present in synovial fluid of patients with rheumatoid arthritis. It induces the expression of chemotactic cytokines (chemokines) such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in synovial cells.
Based on our recent finding that reactive oxygen intermediates play important roles in mediating TNF-α action, we examined the effect of an antioxidant flavonoid, quercetin, on TNF-α-induced expression of IL-8 and MCP-1 in cultured human synovial cells. Quercetin suppressed the TNF-α-induced increase in the mRNAs for IL-8 and MCP-1 in a dose dependent manner. H₂O₂-mediated induction of these genes was also inhibited by quercetin. Electrophoretic mobility shift assays revealed that quercetin inhibited the activation of NF-κB by TNF-α.
These results demonstrate for the first time that quercetin suppresses TNF-α-mediated stimulation of IL-8 and MCP-1 expression, at least in part, by inhibiting the activation of NF-κB.