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Innate Immun. 2019 May 3:1753425919844587. doi: 10.1177/1753425919844587. [Epub ahead of print]

NAD metabolites interfere with proliferation and functional properties of THP-1 cells.

Author information

1
1 Institute of Clinical Immunology, Leipzig University, Germany.
2
2 Department of Molecular Oncology, Leipzig University, Germany.
3
3 Centre for Paediatric Research Leipzig (CPL), Leipzig University, Germany.
4
4 Institute of Metabolism and Systems Research, University of Birmingham, UK.
5
5 Institute of Biology, Leipzig University, Germany.

Abstract

Over the past few years the NAD-related compounds nicotinamide (NAM), nicotinamide riboside (NR) and 1-methylnicotinamide (MNA) have been established as important molecules in signalling pathways that contribute to metabolic functions of many cells, including those of the immune system. Among immune cells, monocytes/macrophages, which are the major players of inflammatory processes, are especially susceptible to the anti-inflammatory action of NAM. Here we asked whether NAM and the two other compounds have the potential to regulate differentiation and LPS-induced biological answers of the monocytic cell line THP-1. We show that treatment of THP-1 cells with NAM, NR and MNA resulted in growth retardation accompanied by enrichment of cells in the G0/G1-phase independent of p21 and p53. NAM and NR caused an increase in intracellular NAD concentrations and SIRT1 and PARP1 mRNA expression was found to be enhanced. The compounds failed to up-regulate the expression of the cell surface differentiation markers CD38, CD11b and CD14. They modulated the reactive oxygen species production and primed the cells to respond less effectively to the LPS induced TNF-α production. Our data show that the NAD metabolites interfere with early events associated with differentiation of THP-1 cells along the monocytic path and that they affect LPS-induced biological responses of the cell line.

KEYWORDS:

1-Methylnicotinamide; THP-1 differentiation; nicotinamide; nicotinamide riboside; pro-inflammatory cytokines; reactive oxygen species

PMID:
31053044
DOI:
10.1177/1753425919844587

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