| First Author | Mounier R | Year | 2013 |
| Journal | Cell Metab | Volume | 18 |
| Issue | 2 | Pages | 251-64 |
| PubMed ID | 23931756 | Mgi Jnum | J:200988 |
| Mgi Id | MGI:5510613 | Doi | 10.1016/j.cmet.2013.06.017 |
| Citation | Mounier R, et al. (2013) AMPKalpha1 regulates macrophage skewing at the time of resolution of inflammation during skeletal muscle regeneration. Cell Metab 18(2):251-64 |
| abstractText | Macrophages control the resolution of inflammation through the transition from a proinflammatory (M1) to an anti-inflammatory (M2) phenotype. Here, we present evidence for a role of AMPKalpha1, a master regulator of energy homeostasis, in macrophage skewing that occurs during skeletal muscle regeneration. Muscle regeneration was impaired in AMPKalpha1(-/-) mice. In vivo loss-of-function (LysM-Cre;AMPKalpha1(fl/fl) mouse) and rescue (bone marrow transplantation) experiments showed that macrophagic AMPKalpha1 was required for muscle regeneration. Cell-based experiments revealed that AMPKalpha1(-/-) macrophages did not fully acquire the phenotype or the functions of M2 cells. In vivo, AMPKalpha1(-/-) leukocytes did not acquire the expression of M2 markers during muscle regeneration. Skewing from M1 toward M2 phenotype upon phagocytosis of necrotic and apoptotic cells was impaired in AMPKalpha1(-/-) macrophages and when AMPK activation was prevented by the inhibition of its upstream activator, CaMKKbeta. In conclusion, AMPKalpha1 is crucial for phagocytosis-induced macrophage skewing from a pro- to anti-inflammatory phenotype at the time of resolution of inflammation. |
