Suppression of lipopolysaccharide-induced nuclear factor-κB activity by theaflavin-3,3'-digallate from black tea and other polyphenols through down-regulation of IκB kinase activity in macrophages
Journal
Biochemical Pharmacology
Journal Volume
59
Journal Issue
4
Pages
357-367
Date Issued
2000
Author(s)
Abstract
We investigated the inhibition of IκB 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-β-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 IκBα and IκBβ 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 IκB from the cytosolic fraction, inhibited nuclear factor-κB (NFκB) 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 NFκB through inhibition of IKK activity. Copyright (C) 2000 Elsevier Science Inc.
Subjects
IκB kinase; Inducible nitric oxide synthase; Inhibitor κB; Macrophage; Nuclear factor-κB; RAW 264.7; Theaflavin-3,3'-digallate
SDGs
Other Subjects
casuarinin; epigallocatechin gallate; geraniin; glucose pentagallate; immunoglobulin enhancer binding protein; lipopolysaccharide; nitric oxide synthase; phosphotransferase; polyphenol; procyanidin; theaflavin; theaflavine 3 gallate; theaflavine 3' gallate; theaflavine digallate; thearubigin; unclassified drug; animal cell; article; controlled study; cytotoxicity; dose response; electrophoretic mobility; enzyme activity; enzyme induction; macrophage; macrophage activation; nonhuman; priority journal; Animals; Antioxidants; Biflavonoids; Catechin; Cells, Cultured; Down-Regulation; Enzyme Inhibitors; Flavonoids; Gallic Acid; Gene Expression; Glucosides; Hydrolyzable Tannins; I-kappa B Kinase; Lipopolysaccharides; Macrophages; Mice; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Phenols; Phosphorylation; Polymers; Protein-Serine-Threonine Kinases; Tannins; Tea
Type
journal article