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

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.

CD38 in the age of COVID-19: a medical perspective

“…In addition to being a surface cell differentiation and activation marker, it was later observed that CD38 can induce the release of different cytokines after specific agonistic monoclonal antibody (mAb) ligation (61). Conversely, it was observed that IFN-c alone induces CD38 in human macrophage/monocytes (67) and that vitamin D causes myeloid cells to express surface markers of monocytic cell differentiation (e.g., CD38, CD14, and CD11b), converting macrophages into potent immunosuppressive cells (68). CD38 activity in human macrophages is prevalently detected intracellularly, with its primary function being 1) the performance of cADPR and NAADP for Ca 21 regulation; 2) the contribution to inflammatory cytokine secretion, and 3) cooperation in reprogrammed metabolic adaptations (e.g., increased glycolytic activity).…”

Pharmacology and Potential Implications of Nicotinamide Adenine Dinucleotide Precursors

“…Recently, NR was reported to reduce the proliferation and activation of liver progenitor cells involved in liver tumour heterogeneity [ 188 ]. NR treatment can also reduce the size of the established liver tumour [ 189 ]. Increasing NAD + levels have been shown to play an important role in the prevention of liver cancer and pancreatic cancer in mice [ 188 , 190 , 191 ].…”

Modulatory Effect of Nicotinic Acid on the Metabolism of Caco-2 Cells Exposed to IL-1β and LPS

“…Among all the effects of NA, different studies proved its role in ameliorating the inflammatory process [15,16]. Moreover, it has been demonstrated that nicotinic acid metabolites, such as nicotinamide, have an antioxidant and anti-inflammatory effect, on human primary monocytes and monocyte-derived macrophages [17] and it has been evidenced that these metabolites could interfere with early events associated to the differentiation of monocytic cell line THP-1 and that they affect LPS-induced biological responses of the cell line [18]. In the present study, an in vitro model was used to study NA effects on intestinal inflammation.…”