Author Faculty (Discipline)

Nursing

Document Type

Article

Publication Date

1-8-2018

JOURNAL

International Journal of Tryptophan Research

VOLUME NUMBER

11

PAGE NUMBERS

1-8

ISSN

1178-6469

Embargo Period

1-24-2019

ANZSRC / FoR Code

119999 Medical and Health Sciences not elsewhere classified

Reportable Items (HERDC/ERA)

C1

Abstract

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.

Link to publisher version (DOI)

https://doi.org/10.1177/1178646917751636

Comments

Copyright © 2018 Ross Grant

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.


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