(-)-Epigallocatechin gallate suppresses indoleamine 2,3-dioxygenase expression in murine dendritic cells: evidences for the COX-2 and STAT1 as potential targets.
(-)-Epigallocatechin gallate (EGCG), a major form of tea catechin, is suggested to exhibit antioxidant and anticyclooxygenase properties. Indoleamine 2,3-dioxygenase (IDO), as a key enzyme in T cell suppression and induction of immune tolerance to tumor, is expressed in various cell types. In the present study, we investigated whether EGCG could suppress the expression of IDO in murine bone marrow-derived dendritic cells (BMDCs) stimulated with IFN-gamma. We obtained evidence that EGCG suppresses the expression and activity of IDO and significantly recovers the IDO-dependent T cell suppression. To determine whether these inhibitory effect of EGCG is associated with the alteration of the signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor 1 (IRF-1) as well as COX-2 expression, BMDCs were pretreated with various concentrations of EGCG. We found that EGCG inhibited the activation and binding of STAT1 to the IRF-1 promoter in response to IFN-gamma. Furthermore, EGCG inhibited the expression of COX-2 and the production of PGE(2). Based on our results, this study may account that EGCG could inhibit IDO expression by down-regulation of STAT1 activation and COX-2 expression in IFN-gamma-stimulated murine DCs.
Jeong
Young-Il
YI
Department of Microbiology, Pusan National University College of Natural Science, Busan, Republic of Korea.
Jung
In Duk
ID
Lee
Jun Sik
JS
Lee
Chang-Min
CM
Lee
Jae-Dong
JD
Park
Yeong-Min
YM
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology*; D015536:Down-Regulation; D004790:Enzyme Induction / Q000187:drug effects; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D007371:Interferon-gamma; D002392:Catechin; C045651:epigallocatechin gallate; D051546:Cyclooxygenase 2