Quercetin, a bioflavonoid, inhibits the induction of interleukin 8 and monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha in cultured human synovial cells.
OBJECTIVE
Tumor necrosis factor (TNF)-alpha is present in synovial fluid of patients with rheumatoid arthritis. It induces the expression of proinflammatory cytokines in synovial cells. Based on our recent finding that reactive oxygen intermediates play important roles in mediating TNF-alpha action, we examined the effect of an antioxidant bioflavonoid, quercetin, on TNF-alpha induced expression of interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in cultured human synovial cells.


METHODS
The amounts of mRNA for IL-8 and MCP-1 were determined by Northern blot analysis. Electrophoretic mobility shift assays (EMSA) were performed for the detection of a transcription factor, nuclear factor-kappa B (NF-kappa B).


RESULTS
Addition of quercetin suppressed TNF-alpha induced increase in the mRNA for IL-8 and MCP-1 in a dose dependent manner. Quercetin did not affect the stability of these mRNA. H2O2 mediated induction of IL-8 and MCP-1 genes was also inhibited by quercetin. EMSA revealed that quercetin inhibited the activation of NF-kappa B by TNF-alpha.


CONCLUSIONS
Quercetin suppresses TNF-alpha mediated stimulation of IL-8 and MCP-1 expression, at least in part, by inhibiting the activation of NF-kappa B.
Sato
M
M
Department of Endocrinology and Metabolism, Nagoya University, Japan.
Miyazaki
T
T
Kambe
F
F
Maeda
K
K
Seo
H
H
D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015152:Blotting, Northern; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D015342:DNA Probes / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D018932:Chemokine CCL2; D015342:DNA Probes; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D011794:Quercetin; D006861:Hydrogen Peroxide