Bioflavonoid quercetin inhibits interleukin-1-induced transcriptional expression of monocyte chemoattractant protein-1 in glomerular cells via suppression of nuclear factor-kappa B

Flavonoids are semiessential food components that possess anti-inflammatory properties. This report describes a novel potential of bioflavonoid querce tin as an inhibitor of monocyte chemoattractant protein-1 (MCP-1) in glomer ular cells. Cultured mesangial cells as well as isolated glomeruli expresse d MCP-1 mRNA in response to interleukin-1 beta (IL-1 beta) Quercetin dramat ically inhibited the cytokine-triggered MCP-1 expression. To explore the me chanisms involved, effects of quercetin on the putative transcriptional act ivators of MCP-1, nuclear factor-kappa B (NF-kappa B) and activator protein -1 (AP-1), were examined. Exposure of the cells to IL-1 beta caused activat ion of NF-kappa B without significant upregulation of AP-1 activity. NF-kap pa B inhibitor MG132 diminished the IL-1-induced expression of MCP-1 in mes angial cells find isolated glomeruli, whereas c-Jun/AP-1 inhibitor curcumin did not affect this process. Consistently, NF-kappa B-inactive mesangial c ells expressing a super-repressor mutant of I kappa B alpha showed blunted expression of MCP-1 by IL-1 beta. In contrast, AP-1-inactive mesangial cell s expressing a dominant-negative mutant of c-Jun exhibited the same level o f MCP-1 mRNA as that in control cells. These results suggest that: (1) quer cetin has the ability to attenuate activation of NF-kappa B; and (2) it inh ibits IL-1-triggered MCP-1 expression via suppression of NF-kappa B, but no t AP-1, in glomerular cells.