Interleukin-1 enhances indoleamine 2,3-dioxygenase activity by increasing specific mRNA 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-1 (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; IL-1 alone had no effect on untreated THP-1 cells. Because IDO gene regulation might differ between immature THP-1 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.
Hu
B
B
Department of Microbiology, Miami University, Oxford, OH 45056, USA.
Hissong
B D
BD
Carlin
J M
JM
D001483:Base Sequence; D002478:Cells, Cultured; D004357:Drug Synergism; D004790:Enzyme Induction; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D011994:Recombinant Proteins; D014366:Tryptophan Oxygenase / Q000096:biosynthesis / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase