| First Author | Liu L | Year | 2016 |
| Journal | Proc Natl Acad Sci U S A | Volume | 113 |
| Issue | 6 | Pages | 1564-9 |
| PubMed ID | 26811453 | Mgi Jnum | J:230492 |
| Mgi Id | MGI:5762715 | Doi | 10.1073/pnas.1518000113 |
| Citation | Liu L, et al. (2016) Proinflammatory signal suppresses proliferation and shifts macrophage metabolism from Myc-dependent to HIF1alpha-dependent. Proc Natl Acad Sci U S A 113(6):1564-9 |
| abstractText | As a phenotypically plastic cellular population, macrophages change their physiology in response to environmental signals. Emerging evidence suggests that macrophages are capable of tightly coordinating their metabolic programs to adjust their immunological and bioenergetic functional properties, as needed. Upon mitogenic stimulation, quiescent macrophages enter the cell cycle, increasing their bioenergetic and biosynthetic activity to meet the demands of cell growth. Proinflammatory stimulation, however, suppresses cell proliferation, while maintaining a heightened metabolic activity imposed by the production of bactericidal factors. Here, we report that the mitogenic stimulus, colony-stimulating factor 1 (CSF-1), engages a myelocytomatosis viral oncogen (Myc)-dependent transcriptional program that is responsible for cell cycle entry and the up-regulation of glucose and glutamine catabolism in bone marrow-derived macrophages (BMDMs). However, the proinflammatory stimulus, lipopolysaccharide (LPS), suppresses Myc expression and cell proliferation and engages a hypoxia-inducible factor alpha (HIF1alpha)-dependent transcriptional program that is responsible for heightened glycolysis. The acute deletion of Myc or HIF1alpha selectively impaired the CSF-1- or LPS-driven metabolic activities in BMDM, respectively. Finally, inhibition of glycolysis by 2-deoxyglucose (2-DG) or genetic deletion of HIF1alpha suppressed LPS-induced inflammation in vivo. Our studies indicate that a switch from a Myc-dependent to a HIF1alpha-dependent transcriptional program may regulate the robust bioenergetic support for an inflammatory response, while sparing Myc-dependent proliferation. |
