The inhibitory action of quercetin on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells.
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.
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Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Chakravortty
D
D
Sugiyama
T
T
Koide
N
N
Takahashi
K
K
Mori
I
I
Yoshida
T
T
Yokochi
T
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D015536:Down-Regulation; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors; D015151:Immunoblotting; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010766:Phosphorylation; D011794:Quercetin / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
D000975:Antioxidants; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D007371:Interferon-gamma; D011794:Quercetin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases