PMID- 10541287
OWN - NLM
STAT- MEDLINE
DCOM- 19991118
LR  - 20210518
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 10
IP  - 11
DP  - 1999 Nov
TI  - Bioflavonoid quercetin inhibits interleukin-1-induced transcriptional expression 
      of monocyte chemoattractant protein-1 in glomerular cells via suppression of 
      nuclear factor-kappaB.
PG  - 2290-6
AB  - 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.
FAU - Ishikawa, Y
AU  - Ishikawa Y
AD  - Department of Medicine, University College London Medical School, United Kingdom.
FAU - Sugiyama, H
AU  - Sugiyama H
FAU - Stylianou, E
AU  - Stylianou E
FAU - Kitamura, M
AU  - Kitamura M
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor AP-1)
RN  - 9IKM0I5T1E (Quercetin)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*antagonists & inhibitors
MH  - Interleukin-1/*pharmacology
MH  - Kidney Glomerulus/*drug effects/metabolism
MH  - Male
MH  - NF-kappa B/*antagonists & inhibitors/physiology
MH  - Quercetin/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transcription Factor AP-1/antagonists & inhibitors/physiology
MH  - Transcription, Genetic/drug effects
EDAT- 1999/11/30 00:00
MHDA- 1999/11/30 00:01
CRDT- 1999/11/30 00:00
PHST- 1999/11/30 00:00 [pubmed]
PHST- 1999/11/30 00:01 [medline]
PHST- 1999/11/30 00:00 [entrez]
AID - 10.1681/ASN.V10112290 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 1999 Nov;10(11):2290-6. doi: 10.1681/ASN.V10112290.