Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling
NAD<sup>+</sup> 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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-03-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/13/5/455 |
| _version_ | 1797264753310040064 |
|---|---|
| author | Jing Wu Maximilian Bley Russell S. Steans Allison M. Meadows Rebecca D. Huffstutler Rong Tian Julian L. Griffin Michael N. Sack |
| author_facet | Jing Wu Maximilian Bley Russell S. Steans Allison M. Meadows Rebecca D. Huffstutler Rong Tian Julian L. Griffin Michael N. Sack |
| author_sort | Jing Wu |
| collection | DOAJ |
| description | NAD<sup>+</sup> 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. |
| first_indexed | 2024-04-25T00:33:54Z |
| format | Article |
| id | doaj.art-fe56789b6c00446ca9c2cb4d5c2d77d6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-25T00:33:54Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fe56789b6c00446ca9c2cb4d5c2d77d62024-03-12T16:41:47ZengMDPI AGCells2073-44092024-03-0113545510.3390/cells13050455Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 SignalingJing Wu0Maximilian Bley1Russell S. Steans2Allison M. Meadows3Rebecca D. Huffstutler4Rong Tian5Julian L. Griffin6Michael N. Sack7Laboratory 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, USALaboratory 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, USALaboratory 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, USALaboratory 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, USACardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USAMitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA 98195, USADepartment of Biochemistry, Cambridge University, Cambridge CB2 1QW, UKLaboratory 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, USANAD<sup>+</sup> 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.https://www.mdpi.com/2073-4409/13/5/455chemotaxismacrophage migrationNAD<sup>+</sup> boostingnicotinamide ribosideprostaglandin E2SIRT3 |
| spellingShingle | Jing Wu Maximilian Bley Russell S. Steans Allison M. Meadows Rebecca D. Huffstutler Rong Tian Julian L. Griffin Michael N. Sack Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling Cells chemotaxis macrophage migration NAD<sup>+</sup> boosting nicotinamide riboside prostaglandin E2 SIRT3 |
| title | Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling |
| title_full | Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling |
| title_fullStr | Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling |
| title_full_unstemmed | Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling |
| title_short | Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling |
| title_sort | nicotinamide riboside augments human macrophage migration via sirt3 mediated prostaglandin e2 signaling |
| topic | chemotaxis macrophage migration NAD<sup>+</sup> boosting nicotinamide riboside prostaglandin E2 SIRT3 |
| url | https://www.mdpi.com/2073-4409/13/5/455 |
| work_keys_str_mv | AT jingwu nicotinamideribosideaugmentshumanmacrophagemigrationviasirt3mediatedprostaglandine2signaling AT maximilianbley nicotinamideribosideaugmentshumanmacrophagemigrationviasirt3mediatedprostaglandine2signaling AT russellssteans nicotinamideribosideaugmentshumanmacrophagemigrationviasirt3mediatedprostaglandine2signaling AT allisonmmeadows nicotinamideribosideaugmentshumanmacrophagemigrationviasirt3mediatedprostaglandine2signaling AT rebeccadhuffstutler nicotinamideribosideaugmentshumanmacrophagemigrationviasirt3mediatedprostaglandine2signaling AT rongtian nicotinamideribosideaugmentshumanmacrophagemigrationviasirt3mediatedprostaglandine2signaling AT julianlgriffin nicotinamideribosideaugmentshumanmacrophagemigrationviasirt3mediatedprostaglandine2signaling AT michaelnsack nicotinamideribosideaugmentshumanmacrophagemigrationviasirt3mediatedprostaglandine2signaling |