Journal
BIOCHEMICAL PHARMACOLOGY
Volume 59, Issue 4, Pages 357-367Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0006-2952(99)00335-4
Keywords
theaflavin-3,3 '-digallate; I kappa B kinase; nuclear factor-kappa B; inhibitor kappa B; inducible nitric oxide synthase; macrophage; RAW 264.7
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We investigated the inhibition of I kappa B 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 I kappa B alpha and I kappa B beta 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 I kappa B from the cytosolic fraction, inhibited nuclear factor-kappa B (NF kappa B) 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 NF kappa B through inhibition of IKK activity. BIOCHEM PHARMACOL 59;4:357-367, 2000. (C) 2000 Elsevier Science Inc.
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