INTERLEUKIN-1 ENHANCES INDOLEAMINE 2,3-DIOXYGENASE ACTIVITY BY INCREASING SPECIFIC MESSENGER-RNA EXPRESSION IN HUMAN MONONUCLEAR PHAGOCYTES

The objective of this study was to determine the utility of the THP-1 monocytic leukemia cell line as a model for analyzing molecular mechanisms involved in enhancement of interferon (IFN)-gamma-induced indoleamine dioxygenase (IDO) activity by interleukin-l (IL-1). Following treatment of THP-1 cells with combinations of IFN-gamma and IL-1, IDO activity and IDO mRNA were quantified by HPLC and radioanalytic imaging of RT-PCR products, respectively, IL-1 increased the amount of IDO activity and the expression of IDO mRNA in IFN-treated cells; TL-1 alone had no effect on untreated THP-I cells, Because IDO gene regulation might differ between immature THP-I cells and mature macrophages, experiments were repeated using primary macrophage cultures, IFN-gamma induced IDO activity, and IDO mRNA was expressed in a dose-dependent manner, In the presence of IL-1, 10 times less IFN was required to obtain the same amount of IDO mRNA and IDO activity, Furthermore, IL-1 alone increased IDO mRNA expression, It appears that unlike what was observed in THP-1 cells, IL-1 transcriptionally activates the IDO gene in primary macrophages, However, increases in IDO activity were not observed following treatment with IL-1 alone, Although the THP-1 cell may be used to model cytokine potentiation of IFN-induced IDO activity, some differences in regulation between THP-1 cells and primary macrophage cultures may exist.