p-Coumaric acid inhibits indoleamine 2, 3-dioxygenase expression in murine dendritic cells.
Indoleamine 2, 3-dioxygenase (IDO), a key enzyme that catalyses the initial and rate-limiting step in the degradation of the tryptophan, is simultaneously expressed in murine dendritic cells and macrophages stimulated with interferon-gamma (IFN-gamma). In the present study, we investigated whether p-Coumaric acid (CA), which is suggested to exhibit antioxidant properties, could suppress the functional expression of IDO in murine bone marrow-derived dendritic cells (BMDCs) stimulated with IFN-gamma. Treatment with CA reduced intracellular expression of IDO mRNA and protein levels in IFN-gamma-activated murine BMDCs in vitro and in CD11c(+)CD8alpha(+) DCs of tumor-draining lymph node (TDLN) of tumor-bearing mice in vivo. Consequently, we obtained evidence that CA suppresses the functional activity of IDO, which catalyses oxidative catabolism of tryptophan, and significantly recovers the IDO-dependent T cell suppression. Activation of the signal transducer and activator of transcription 1 (STAT1) is important to be express IDO in IFN-gamma-stimulated murine BMDCs. To determine whether these inhibitory effects of CA are associated with the alteration of the signal transducer and activator of transcription 1 (STAT1) and IFN-gamma-inducible, dsRNA-activated serine/threonine protein kinase (PKR), BMDCs were pretreated with various concentrations of CA. We found that CA inhibited the activation of STAT1 in response to IFN-gamma. Based on our results, this study may account that CA could inhibit IDO expression by down-regulation of STAT1 activation in IFN-gamma-stimulated murine DCs.
Kim
Sang Il
SI
Department of Obstetrics and Gynecology, College of Medicine, Pusan National University, Ami-Dong 1-10, Seo-Gu, Busan, South Korea.
Jeong
Young-Il
YI
Jung
In Duk
ID
Lee
Jun Sik
JS
Lee
Chang-Min
CM
Yoon
Man-Soo
MS
Seong
Eun-Young
EY
Kim
Jong-Il
JI
Lee
Jae-Dong
JD
Park
Yeong-Min
YM
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011422:Propionates; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D003373:Coumaric Acids; D007155:Immunologic Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011422:Propionates; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D007371:Interferon-gamma; D010047:Ovalbumin; C495469:p-coumaric acid