PMID- 9292787 OWN - NLM STAT- MEDLINE DCOM- 19971016 LR - 20131121 IS - 0315-162X (Print) IS - 0315-162X (Linking) VI - 24 IP - 9 DP - 1997 Sep TI - 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. PG - 1680-4 AB - 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. CONCLUSION: 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. FAU - Sato, M AU - Sato M AD - Department of Endocrinology and Metabolism, Nagoya University, Japan. FAU - Miyazaki, T AU - Miyazaki T FAU - Kambe, F AU - Kambe F FAU - Maeda, K AU - Maeda K FAU - Seo, H AU - Seo H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Canada TA - J Rheumatol JT - The Journal of rheumatology JID - 7501984 RN - 0 (Chemokine CCL2) RN - 0 (DNA Probes) RN - 0 (Interleukin-8) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9IKM0I5T1E (Quercetin) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - Arthritis, Rheumatoid/drug therapy/metabolism/pathology MH - Blotting, Northern MH - Cells, Cultured MH - Chemokine CCL2/*biosynthesis/genetics MH - DNA Probes/chemistry MH - Humans MH - Hydrogen Peroxide/antagonists & inhibitors/pharmacology MH - Interleukin-8/*biosynthesis/genetics MH - NF-kappa B/antagonists & inhibitors MH - Quercetin/*pharmacology MH - RNA, Messenger/*biosynthesis MH - Recombinant Proteins/pharmacology MH - Synovial Membrane/drug effects/*metabolism/pathology MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/pharmacology EDAT- 1997/09/18 00:00 MHDA- 1997/09/18 00:01 CRDT- 1997/09/18 00:00 PHST- 1997/09/18 00:00 [pubmed] PHST- 1997/09/18 00:01 [medline] PHST- 1997/09/18 00:00 [entrez] PST - ppublish SO - J Rheumatol. 1997 Sep;24(9):1680-4.