Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling

Jing Wu; Maximilian Bley; Russell S. Steans; Allison M. Meadows; Rebecca D. Huffstutler; Rong Tian; Julian L. Griffin; Michael N. Sack

doi:10.3390/cells13050455

Cells (Mar 2024)

Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling

Jing Wu,
Maximilian Bley,
Russell S. Steans,
Allison M. Meadows,
Rebecca D. Huffstutler,
Rong Tian,
Julian L. Griffin,
Michael N. Sack

Affiliations

Jing Wu: Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg. 10-CRC, Room 5-3342, 10 Center Drive, Bethesda, MD 20892, USA
Maximilian Bley: Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg. 10-CRC, Room 5-3342, 10 Center Drive, Bethesda, MD 20892, USA
Russell S. Steans: Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg. 10-CRC, Room 5-3342, 10 Center Drive, Bethesda, MD 20892, USA
Allison M. Meadows: Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg. 10-CRC, Room 5-3342, 10 Center Drive, Bethesda, MD 20892, USA
Rebecca D. Huffstutler: Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Rong Tian: Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
Julian L. Griffin: Department of Biochemistry, Cambridge University, Cambridge CB2 1QW, UK
Michael N. Sack: Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg. 10-CRC, Room 5-3342, 10 Center Drive, Bethesda, MD 20892, USA

DOI: https://doi.org/10.3390/cells13050455
Journal volume & issue: Vol. 13, no. 5
p. 455

Abstract

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NAD+ boosting via nicotinamide riboside (NR) confers anti-inflammatory effects. However, its underlying mechanisms and therapeutic potential remain incompletely defined. Here, we showed that NR increased the expression of CC-chemokine receptor 7 (CCR7) in human M1 macrophages by flow cytometric analysis of cell surface receptors. Consequently, chemokine ligand 19 (CCL19, ligand for CCR7)-induced macrophage migration was enhanced following NR administration. Metabolomics analysis revealed that prostaglandin E2 (PGE2) was increased by NR in human monocytes and in human serum following in vivo NR supplementation. Furthermore, NR-mediated upregulation of macrophage migration through CCL19/CCR7 was dependent on PGE2 synthesis. We also demonstrated that NR upregulated PGE2 synthesis through SIRT3-dependent post-transcriptional regulation of cyclooxygenase 2 (COX-2). The NR/SIRT3/migration axis was further validated using the scratch-test model where NR and SIRT3 promoted more robust migration across a uniformly disrupted macrophage monolayer. Thus, NR-mediated metabolic regulation of macrophage migration and wound healing may have therapeutic potential for the topical management of chronic wound healing.

Published in Cells

ISSN: 2073-4409 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Cytology
Website: https://www.mdpi.com/journal/cells

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