Bioflavonoid quercetin inhibits interleukin-1-induced transcriptional expression of monocyte chemoattractant protein-1 in glomerular cells via suppression of nuclear factor-kappaB.
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-1beta (IL-1beta). 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-kappaB (NF-kappaB) and activator protein-1 (AP-1), were examined. Exposure of the cells to IL-1beta caused activation of NF-kappaB without significant upregulation of AP-1 activity. NF-kappaB 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-kappaB-inactive mesangial cells expressing a super-repressor mutant of IkappaBalpha showed blunted expression of MCP-1 by IL-1beta. 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-kappaB; and (2) it inhibits IL-1-triggered MCP-1 expression via suppression of NF-kappaB, but not AP-1, in glomerular cells.
Ishikawa
Y
Y
Department of Medicine, University College London Medical School, United Kingdom.
Sugiyama
H
H
Stylianou
E
E
Kitamura
M
M
D000818:Animals; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors*; D007375:Interleukin-1 / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
D018932:Chemokine CCL2; D007375:Interleukin-1; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D011794:Quercetin