AMPKα1 Regulates Macrophage Skewing at the Time of Resolution of Inflammation during Skeletal Muscle Regeneration.. AMPKα1 Regulates Macrophage Skewing at the Time of Resolution of Inflammation during Skeletal Muscle Regeneration.: AMPKα1 regulates macrophage skewing

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Mounier, Rémi | Théret, Marine | Arnold, Ludovic | Cuvellier, Sylvain | Bultot, Laurent | Göransson, Olga | Sanz, Nieves | Ferry, Arnaud | Sakamoto, Kei | Foretz, Marc | Viollet, Benoit | Chazaud, Bénédicte

Edité par CCSD ; Elsevier -

International audience. 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;AMPKα1(fl/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.

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