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

Abstract

Flavonoids are semiessential food components that possess anti- inflammatory properties. This report describes a novel potential of bioflavonoid quercetin as an inhibitor of monocyte chemoattractant protein-1 (MCP-1) in glomerular cells. Cultured mesangial cells as well as isolated glomeruli expressed MCP-1 mRNA in response to interleukin-1β (IL-1β). Quercetin dramatically inhibited the cytokine-triggered MCP-1 expression. To explore the mechanisms involved, effects of quercetin on the putative transcriptional activators of MCP-1, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), were examined. Exposure of the cells to IL-1β caused activation of NF-κB without significant upregulation of AP-1 activity. NF-κB inhibitor MG132 diminished the IL-1-induced expression of MCP-1 in mesangial cells and isolated glomeruli, whereas c-Jun/AP-1 inhibitor curcumin did not affect this process. Consistently, NF-κB-inactive mesangial cells expressing a super-repressor mutant of IκBα showed blunted expression of MCP-1 by IL-1β. In contrast, AP-1-inactive mesangial cells expressing a dominant-negative mutant of c-Jun exhibited the same level of MCP-1 mRNA as that in control cells. These results suggest that: (1) quercetin has the ability to attenuate activation of NF-κB; and (2) it inhibits IL-1-triggered MCP-1 expression via suppression of NF-κB, but not AP-1, in glomerular cells.