Abstract
The effect of quercetin on lipopolysaccharide (LPS)-induced nitric oxide (NO) production was studied. Quercetin pretreatment significantly inhibited NO production in an LPS-stimulated RAW 264.7 murine macrophage cell line. Post-treatment with quercetin partially inhibited NO production. The inhibitory action of quercetin was due to neither the cytotoxic action nor altered LPS binding. The expression of inducible-type NO synthase (iNOS) was markedly down-regulated by quercetin. Quercetin suppressed the release of free nuclear factor (NF)-kappaB by preventing degradation of IkappaB-alpha and IkappaB-beta. Moreover, quercetin blocked the phosphorylation of extracellular signal regulated kinase 1/2 (Erk 1/2), p38, and c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) and, further, the activity of tyrosine kinases in LPS-stimulated RAW cells. Quercetin also inhibited interferon (IFN)-gamma-induced NO production. Taken together, these results indicate that the inhibitory action of quercetin on NO production in LPS- and/or IFN-gamma-stimulated macrophages might be due to abrogation of iNOS protein induction by impairment of a series of intracellular signal pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antioxidants / pharmacology*
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Cell Line
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Down-Regulation
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Enzyme Induction
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Enzyme Inhibitors / pharmacology
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I-kappa B Proteins / antagonists & inhibitors
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Immunoblotting
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In Vitro Techniques
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Interferon-gamma / antagonists & inhibitors
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JNK Mitogen-Activated Protein Kinases
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Lipopolysaccharides / antagonists & inhibitors*
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Lipopolysaccharides / pharmacology
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Macrophages / drug effects
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Macrophages / enzymology
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Macrophages / metabolism*
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Mice
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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NF-kappa B / metabolism
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Nitric Oxide / biosynthesis*
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type II
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Phosphorylation
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Quercetin / pharmacology*
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p38 Mitogen-Activated Protein Kinases
Substances
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Antioxidants
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Enzyme Inhibitors
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I-kappa B Proteins
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Lipopolysaccharides
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NF-kappa B
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Nitric Oxide
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Interferon-gamma
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Quercetin
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase Kinases