PMID- 11502884
OWN - NLM
STAT- MEDLINE
DCOM- 20010906
LR  - 20211203
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 60
IP  - 3
DP  - 2001 Sep
TI  - The green tea polyphenol (-)-epigallocatechin-3-gallate blocks nuclear 
      factor-kappa B activation by inhibiting I kappa B kinase activity in the 
      intestinal epithelial cell line IEC-6.
PG  - 528-33
AB  - The I kappa B kinase complex (IKK) mediates activation of the transcription 
      factor nuclear factor-kappa B (NF-kappa B). We previously showed that green tea 
      polyphenols inhibited endotoxin-mediated tumor necrosis factor-alpha (TNF alpha) 
      production by blocking NF-kappa B activation. In this study, we evaluated whether 
      green tea polyphenols inhibit NF-kappa B by blocking IKK activity. We assessed 
      IKK activity by detecting changes in phosphorylation of an I kappa B 
      alpha-glutathione S-transferase (GST) fusion protein. IEC-6 cells pretreated with 
      an extract of green tea polyphenols (GrTPs; 0--0.4 mg/ml) had diminished TNF 
      alpha-induced IKK and NF-kappa B activity. Of the various GrTPs, 
      (-)-epigallocatechin-3-gallate (EGCG) was the most potent inhibitor. We next 
      examined whether EGCG inhibited activated IKK. In cytosolic extracts of TNF 
      alpha-stimulated cells, EGCG inhibited phosphorylation of I kappa B alpha-GST 
      (IC(50) > 18 microM) consistent with inhibition of IKK activity. Using other 
      polyphenols, we showed that the gallate group was essential for inhibition, and 
      antioxidants were ineffective in blocking activated IKK. Importantly, EGCG 
      decreased IKK activity in cytosolic extracts of NIK transiently transfected 
      cells. This latter finding showed that our findings were not related to 
      nonspecific kinase activity. In conclusion, EGCG is an effective inhibitor of IKK 
      activity. This may explain, at least in part, some of the reported 
      anti-inflammatory and anticancer effects of green tea.
FAU - Yang, F
AU  - Yang F
AD  - Graduate Program in Nutritional Sciences, University of Kentucky and Veterans 
      Administration Medical Center, Lexington, Kentucky, USA.
FAU - Oz, H S
AU  - Oz HS
FAU - Barve, S
AU  - Barve S
FAU - de Villiers, W J
AU  - de Villiers WJ
FAU - McClain, C J
AU  - McClain CJ
FAU - Varilek, G W
AU  - Varilek GW
LA  - eng
GR  - IPO1-NS31220-01A1/NS/NINDS NIH HHS/United States
GR  - KO8-DK02401-01A/DK/NIDDK NIH HHS/United States
GR  - MO1-RR02602/RR/NCRR NIH HHS/United States
GR  - R01-AA010762/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Phenols)
RN  - 0 (Polymers)
RN  - 0 (Tea)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 8R1V1STN48 (Catechin)
RN  - BQM438CTEL (epigallocatechin gallate)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Animals
MH  - Catechin/analogs & derivatives/*pharmacology
MH  - Cell-Free System
MH  - Cells, Cultured
MH  - Enzyme Inhibitors/*pharmacology
MH  - *Flavonoids
MH  - I-kappa B Kinase
MH  - I-kappa B Proteins/*antagonists & inhibitors/metabolism
MH  - Intestinal Mucosa/*drug effects/enzymology/metabolism
MH  - NF-kappa B/*antagonists & inhibitors/metabolism
MH  - Phenols/pharmacology
MH  - Phosphorylation/drug effects
MH  - Polymers/pharmacology
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/drug effects/metabolism
MH  - Rats
MH  - Tea/*chemistry
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2001/08/15 10:00
MHDA- 2001/09/08 10:01
CRDT- 2001/08/15 10:00
PHST- 2001/08/15 10:00 [pubmed]
PHST- 2001/09/08 10:01 [medline]
PHST- 2001/08/15 10:00 [entrez]
PST - ppublish
SO  - Mol Pharmacol. 2001 Sep;60(3):528-33.