AMPKα1 regulates macrophage skewing at the time of resolution of inflammation during skeletal muscle regeneration
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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 AMPKα1, a master regulator of energy homeostasis, in macrophage skewing that occurs during skeletal muscle regeneration. Muscle regeneration was impaired in AMPKα1-/- mice. In vivo loss-of-function (LysM-Cre;AMPKα1fl/fl mouse) and rescue (bone marrow transplantation) experiments showed that macrophagic AMPKα1 was required for muscle regeneration. Cell-based experiments revealed that AMPKα1-/- macrophages did not fully acquire the phenotype or the functions of M2 cells. In vivo, AMPKα1-/- 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 AMPKα1-/- macrophages and when AMPK activation was prevented by the inhibition of its upstream activator, CaMKKβ. In conclusion, AMPKα1 is crucial for phagocytosis-induced macrophage skewing from a pro- to anti-inflammatory phenotype at the time of resolution of inflammation.
Original language | English |
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Journal | Cell Metabolism |
Volume | 18 |
Issue number | 2 |
Pages (from-to) | 251-264 |
Number of pages | 14 |
ISSN | 1550-4131 |
DOIs | |
Publication status | Published - 6 Aug 2013 |
Externally published | Yes |
ID: 239216529