title: Rosmarinic acid inhibits indoleamine 2,3-dioxygenase expression in murine dendritic cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hwa Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Jeong
authors.forename: Tae-Hyung
authors.initials: TH
authors.lastname: Lee
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.forename: Jun Sik
authors.initials: JS
authors.lastname: Lee
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Hwan
authors.initials: H
authors.lastname: Joo
authors.forename: Jae-Dong
authors.initials: JD
authors.lastname: Lee
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
mesh_terms: 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
chemical_list: 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