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  • Title: Rosmarinic acid inhibits indoleamine 2,3-dioxygenase expression in murine dendritic cells.
    Author: Lee HJ, Jeong YI, Lee TH, Jung ID, Lee JS, Lee CM, Kim JI, Joo H, Lee JD, Park YM.
    Journal: Biochem Pharmacol; 2007 May 01; 73(9):1412-21. PubMed ID: 17229401.
    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.
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