title: Niacin and its metabolites as master regulators of macrophage activation.
abstract: Niacin is a broad-spectrum lipid-regulating drug used for clinical therapy of chronic high-grade inflammatory diseases. However, the mechanisms by which either niacin or the byproducts of its catabolism ameliorate these inflammatory diseases are not clear yet. Human circulating monocytes and mature macrophages were used to analyze the effects of niacin and its metabolites (NAM, NUA and 2-Pyr) on oxidative stress, plasticity and inflammatory response by using biochemical, flow cytometry, quantitative real-time PCR and Western blot technologies. Niacin, NAM and 2-Pyr significantly decreased ROS, NO and NOS2 expression in LPS-treated human mature macrophages. Niacin and NAM skewed macrophage polarization toward antiinflammatory M2 macrophage whereas a trend toward proinflammatory M1 macrophage was noted following treatment with NUA. Niacin and NAM also reduced the inflammatory competence of LPS-treated human mature macrophages and promoted bias toward antiinflammatory CD14+CD16++nonclassical human primary monocytes. This study reveals for the first time that niacin and its metabolites possess antioxidant, reprogramming and antiinflammatory properties on human primary monocytes and monocyte-derived macrophages. Our findings imply a new understanding of the mechanisms by which niacin and its metabolites favor a continuous and gradual plasticity process in the human monocyte/macrophage system.
authors: Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, CSIC, Seville, Spain.
authors: Sergio
authors: S
authors: Montserrat-de la Paz
authors: Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, CSIC, Seville, Spain.
authors: M Carmen
authors: MC
authors: Naranjo
authors: Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, CSIC, Seville, Spain.
authors: Sergio
authors: S
authors: Lopez
authors: Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, CSIC, Seville, Spain.
authors: Rocio
authors: R
authors: Abia
authors: Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, CSIC, Seville, Spain.
authors: Francisco J Garcia
authors: FJG
authors: Muriana
authors: Department of Cell Biology, School of Biology, University of Seville, Seville, Spain. Electronic address: bbermudez@us.es.
authors: Beatriz
authors: B
authors: Bermudez
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects; D009525:Niacin / Q000494:pharmacology*; D009536:Niacinamide / Q000494:pharmacology*; D009539:Nicotinic Acids / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D011728:Pyridones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C525085:N-methyl-2-pyridone-5-carboxamide; D009539:Nicotinic Acids; D011728:Pyridones; D017382:Reactive Oxygen Species; D009536:Niacinamide; D009525:Niacin; C002477:nicotinuric acid; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II
keywords: Macrophages; Monocytes; Niacin; Nicotinamide; Nicotinuric acid; Polarization