Niacin and its metabolites as master regulators of macrophage activation

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• 作者：Sergio Montserrat-de la Paz^a ; M. Carmen Naranjo^a ; Sergio Lopez^a ; Rocio Abia^a ; Francisco J. Garcia Muriana^a ; Beatriz Bermudez^b ; ^{bbermudez@us.es}
• 关键词：Niacin ; Nicotinamide ; Nicotinuric acid ; Monocytes ; Macrophages ; Polarization
• 刊名：The Journal of Nutritional Biochemistry
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：39
• 期：Complete
• 页码：40-47
• 全文大小：1515 K
• 卷排序：39

文摘

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.