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-γ (IFN-γ). 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-γ. Treatment with RA reduced intracellular expression of IDO both in IFN-γ-activated BMDCs in vitro and in CD11c+CD8α+ 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-γ-mediated induction of IDO transcription, activation of the signal transducer and activator of transcription 1 (STAT1) is important to be express IDO in IFN-γ-stimulated BMDCs. In this study, we demonstrated that the RA could also suppress IFN-γ-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.