Abstract
We investigated the inhibition of IkappaB kinase (IKK) activity in lipopolysaccharide (LPS)-activated murine macrophages (RAW 264.7 cell line) by various polyphenols including (-)-epigallocatechin-3-gallate, theaflavin, a mixture of theaflavin-3 gallate and theaflavin-3'-gallate, theaflavin-3,3'-digallate (TF-3), pyrocyanidin B-3, casuarinin, geraniin, and penta-O-galloyl-beta-D-glucose (5GG). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other polyphenols. TF-3 strongly inhibited both IKK1 and IKK2 activity and prevented the degradation of IkappaBalpha and IkappaBbeta in activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. Furthermore, geraniin, 5GG, and TF-3 all blocked phosphorylation of IKB from the cytosolic fraction, inhibited nuclear factor-kappaB (NFkappaB) activity, and inhibited increases in inducible nitric oxide synthase levels in activated macrophages. These results suggest that TF-3 may exert its anti-inflammatory and cancer chemopreventive actions by suppressing the activation of NFkappaB through inhibition of IKK activity.
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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Biflavonoids*
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Catechin
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Cells, Cultured
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Down-Regulation
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Enzyme Inhibitors / pharmacology
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Flavonoids*
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Gallic Acid / analogs & derivatives*
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Gallic Acid / pharmacology
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Gene Expression / drug effects
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Glucosides / pharmacology
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Hydrolyzable Tannins*
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I-kappa B Kinase
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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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NF-kappa B / metabolism*
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase / biosynthesis
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type II
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Phenols / pharmacology*
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Phosphorylation
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Polymers / pharmacology*
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Polyphenols
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / metabolism
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Tannins / pharmacology
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Tea / chemistry
Substances
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Antioxidants
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Biflavonoids
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Enzyme Inhibitors
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Flavonoids
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Glucosides
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Hydrolyzable Tannins
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Lipopolysaccharides
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NF-kappa B
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Phenols
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Polymers
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Polyphenols
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Tannins
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Tea
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Nitric Oxide
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theaflavin digallate
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pentagalloylglucose
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Geraniin
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Gallic Acid
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Catechin
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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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Protein Serine-Threonine Kinases
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Chuk protein, mouse
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I-kappa B Kinase
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Ikbkb protein, mouse
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Ikbke protein, mouse