Green tea polyphenol epigallocatechin gallate inhibits cell signaling by inducing SOCS1 gene expression.
Therapeutic effects of green tea involve an inhibitory function of its constituent polyphenol epigallocatechin gallate (EGCG) on cell signaling. The specificity and mechanism(s) by which EGCG inhibits cell signaling have remained unclear. Here, we demonstrate that green tea and EGCG induce suppressor of cytokine signaling 1 (SOCS1) gene expression, a negative regulator of specific cell signaling pathways. In mouse immune cells, EGCG induces SOCS1 expression via an oxidative (superoxide) pathway and activation of the signal transducer and activator of transcription 5 transcription factor. EGCG inhibited SOCS1-regulated cell signaling, but this inhibitory effect was abrogated in cells deficient in SOCS1. These findings identify a mechanism by which EGCG inhibits cell signaling with specificity, mediated by induction of the negative regulator SOCS1.
Ripley
Barry J M
BJ
Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
Fujimoto
Minoru
M
Serada
Satoshi
S
Ohkawara
Tomoharu
T
Nishikawa
Teppei
T
Terabe
Fumitaka
F
Matsukawa
Yuko
Y
Stephanou
Anastasis
A
Knight
Richard A
RA
Isenberg
David A
DA
Latchman
David S
DS
Kishimoto
Tadamitsu
T
Naka
Tetsuji
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D013662:Tea / Q000737:chemistry*; D015854:Up-Regulation / Q000187:drug effects*
D000975:Antioxidants; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013662:Tea; D013481:Superoxides; D002392:Catechin; C045651:epigallocatechin gallate