Boosting NAD +in myeloid cells upregulates Prostaglandin E2 (PGE2) and CC-chemokine receptor 7 (CCR7)-mediated migration via Sirt1-dependent transcriptional regulation

Abstract NAD +-boosting via nicotinamide riboside (NR) confer anti-inflammatory effects. However, underlying mechanisms and therapeutic potential remain incompletely defined. Given +is a co-enzyme in oxidoreductive reactions, metabolomics analysis identified two major metabolites that were increased by NR: inosine Prostaglandin E2 (PGE2). Both PGE2 supplementation blunted IFNβ release, however NR-mediated monocytic downregulation of was dependent on but independent PGE2. Flow cytometric cell surface receptors human M1 macrophage showed NR the expression CC-chemokine receptor 7 (CCR7). Consequently, chemokine ligand 19 (CCL19, for CCR7) - induced migration enhanced response to administration. Furthermore, upregulation through CCL19-CCR7 axis synthesis. We also demonstrated upregulates synthesis Sirt1-dependent transcriptional regulation COX2. metabolic appears modulate disparate myeloid functions distinct signaling intermediates pathways. NHLBI Division Intramural Research