title: Nicotinamide: a vitamin able to shift macrophage differentiation toward macrophages with restricted inflammatory features.
abstract: The differentiation of human monocytes into macrophages is influenced by environmental signals. Here we asked in how far nicotinamide (NAM), a vitamin B3 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-MØ) or macrophage colony-stimulating factor (M-MØ). We found that GM-MØ undergo biochemical, morphological and functional modifications in response to NAM, whereas M-MØ were hardly affected. GM-MØ exposed to NAM acquired an M-MØ-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-κB activity to be diminished. In conclusion, our data show that vitamin B3, when present during the differentiation of monocytes into GM-MØ, interferes with biochemical pathways resulting in strongly reduced pro-inflammatory features.
authors.affiliation: University of Leipzig, Translational Centre for Regenerative Medicine (TRM) Leipzig, Leipzig, Germany University Hospital Leipzig, Institute for Clinical Immunology, Leipzig, Germany University of Leipzig, Institute of Biology, Leipzig, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Weiss
authors.affiliation: University of Leipzig, Translational Centre for Regenerative Medicine (TRM) Leipzig, Leipzig, Germany University Hospital Leipzig, Institute for Clinical Immunology, Leipzig, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Schilling
authors.affiliation: University of Leipzig, Translational Centre for Regenerative Medicine (TRM) Leipzig, Leipzig, Germany University Hospital Leipzig, Institute for Clinical Immunology, Leipzig, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Grahnert
authors.affiliation: University of Leipzig, Translational Centre for Regenerative Medicine (TRM) Leipzig, Leipzig, Germany University Hospital Leipzig, Institute for Clinical Immunology, Leipzig, Germany University of Leipzig, Institute of Biology, Leipzig, Germany.
authors.forename: Valeen
authors.initials: V
authors.lastname: Kölling
authors.affiliation: University Hospital Leipzig, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig, Germany University of Leipzig, LIFE - Leipzig Research Center for Civilization Diseases, Leipzig, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Dorow
authors.affiliation: University Hospital Leipzig, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig, Germany University of Leipzig, LIFE - Leipzig Research Center for Civilization Diseases, Leipzig, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Ceglarek
authors.affiliation: University of Leipzig, Translational Centre for Regenerative Medicine (TRM) Leipzig, Leipzig, Germany University Hospital Leipzig, Institute for Clinical Immunology, Leipzig, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sack
authors.affiliation: University of Leipzig, Institute of Biology, Leipzig, Germany shaus@rz.uni-leipzig.de.
authors.forename: Sunna
authors.initials: S
authors.lastname: Hauschildt
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015777:Eicosanoids / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009243:NAD; D016328:NF-kappa B / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014803:Vitamin B Complex / Q000378:metabolism / Q000494:pharmacology
chemical_list: D015777:Eicosanoids; D016328:NF-kappa B; D009243:NAD; D014803:Vitamin B Complex; D009536:Niacinamide; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Inflammation; LPS; NF-κB; macrophages; nicotinamide