Indoleamine 2,3-Dioxygenase Activity Increases NAD+ Production in IFN-γ–Stimulated Human Primary Mononuclear Cells:

International Journal of Tryptophan Research

Ross SGrant¹ 

关键词: monocyte;    macrophage;    tryptophan;    NAD+;    indoleamine 2;    3-dioxygenase;    PARP;   

DOI  :  10.1177/1178646917751636

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

IFN-γ activation of mononuclear phagocytes significantly increases indoleamine 2,3-dioxygenase (IDO) and flux through the kynurenine pathway (KP). However, the effect of IDO on NAD+ synthesis, the end product of KP metabolism, is unknown. To investigate this, primary human peripheral blood mononuclear cells were cultured up to 10 days and activated with IFN-γ in the presence or absence of a poly(ADP-ribose) polymerase (PARP) inhibitor. Day 10 macrophages had significantly higher NAD+ levels compared with monocytes. IFN-γ activation of macrophages resulted in the highest induction of IDO but decreased intracellular NAD+ concentrations at both 24 and 48 hours. However, IFN-γ activation of both day 6 and day 10 macrophages in the presence of a PARP inhibitor resulted in significantly higher intracellular NAD+ levels at 24 hours. This study provides evidence for the first time that an immune-mediated increase in IDO activity increases NAD+ biosynthesis concomitantly with an increase in NAD+ catabolism in primary human macrophages.

【 授权许可】

CC BY