Rosmarinic 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 rosmarinic acid (RA), which is suggested to exhibit anti-oxidant and anti-cyclooxygenase properties, could suppress the functional expression of IDO in murine bone marrow-derived dendritic cells (BMDCs) stimulated with IFN-gamma. Treatment with RA reduced intracellular expression of IDO both in IFN-gamma-activated BMDCs in vitro and in CD11c(+)CD8alpha(+) DCs in vivo tumor-bearing mice model. Consequently, we obtained evidence that RA suppresses the functional activity of IDO and blocks the IDO-dependent T cell suppression. In IFN-gamma-mediated induction of IDO transcription, activation of the signal transducer and activator of transcription 1 (STAT1) is important to be express IDO in IFN-gamma-stimulated BMDCs. In this study, we demonstrated that the RA could also suppress IFN-gamma-induced STAT1 activation. These novel findings provide a new insight into that RA as a pharmacological and transcriptional inhibitor of IDO is worthy of clinical application as well as further investigation for IDO regulation.
Lee
Hwa Jung
HJ
Department of Microbiology and Immunology, National Research Laboratory of Dendritic Cell Differentiation & Regulation, Medical Research Institute, College of Medicine, Pusan National University, Ami-dong 1-10, Seo-Gu, Pusan 602-739, South Korea.
Jeong
Young-Il
YI
Lee
Tae-Hyung
TH
Jung
In Duk
ID
Lee
Jun Sik
JS
Lee
Chang-Min
CM
Kim
Jong-Il
JI
Joo
Hwan
H
Lee
Jae-Dong
JD
Park
Yeong-Min
YM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001854:Bone Marrow Cells; D002934:Cinnamates / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology; D053630:Depsides / Q000494:pharmacology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D050856:Interferon Regulatory Factor-1 / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D008198:Lymph Nodes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000201:enzymology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D000097123:Rosmarinic Acid
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002934:Cinnamates; D053630:Depsides; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma; D050794:STAT1 Transcription Factor; D000097123:Rosmarinic Acid