Details

Autor(en) / Beteiligte

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

Titel

AMPKα1 Regulates Macrophage Skewing at the Time of Resolution of Inflammation during Skeletal Muscle Regeneration

Ist Teil von

• Cell metabolism, 2013-08, Vol.18 (2), p.251-264

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Macrophagic AMPKα1 is required for proper and complete skeletal muscle regeneration•In vitro AMPKα1−/− macrophages do not acquire M2 phenotype and functions•In vivo AMPKα1−/− macrophages do not acquire M2 profile during muscle regeneration•Apoptotic cell phagocytosis, a skewing signal, is lower in AMPKα1−/− macrophages