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.