Journal
INNATE IMMUNITY
Volume 21, Issue 8, Pages 813-826Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1753425915602545
Keywords
Inflammation; LPS; macrophages; NF-B; nicotinamide
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Funding
- Translational Center for Regenerative Medicine (TRM), Leipzig [BMBF 1315883]
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The differentiation of human monocytes into macrophages is influenced by environmental signals. Here we asked in how far nicotinamide (NAM), a vitamin B-3 derivative known to play a major role in nicotinamide adenine dinucleotide (NAD)-mediated signaling events, is able to modulate monocyte differentiation into macrophages developed in the presence of granulocyte macrophage colony-stimulating factor (GM-MO) or macrophage colony-stimulating factor (M-MO). We found that GM-MO undergo biochemical, morphological and functional modifications in response to NAM, whereas M-MO were hardly affected. GM-MO exposed to NAM acquired an M-MO-like structure while the LPS-induced production of pro-inflammatory cytokines and COX-derived eicosanoids were down-regulated. In contrast, NAM had no effect on the production of IL-10 or the cytochrome P450-derived eicosanoids. Administration of NAM enhanced intracellular NAD concentrations; however, it did not prevent the LPS-mediated drain on NAD pools. In search of intracellular molecular targets of NAM known to be involved in LPS-induced cytokine and eicosanoid synthesis, we found NF-B activity to be diminished. In conclusion, our data show that vitamin B-3, when present during the differentiation of monocytes into GM-MO, interferes with biochemical pathways resulting in strongly reduced pro-inflammatory features.
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