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

Rémi Mounier 1 Marine Théret 1 Ludovic Arnold 2 Sylvain Cuvellier 1 Laurent Bultot 3 Olga Göransson 4 Nieves Sanz 1 Arnaud Ferry 5 Kei Sakamoto 3 Marc Foretz 1 Benoit Viollet 1 Bénédicte Chazaud 1, * Remi Mounier 6
* Auteur correspondant
1 IC UM3 (UMR 8104 / U1016) - Institut Cochin
2 Immunité et Infection
3 Nestlé Institute of Health Sciences SA [Lausanne, Switzerland]
4 Department of Experimental Medical Sciences [Lund, Sweden]
5 Institut de Myologie
6 UMR_S567 / UMR 8104 - Institut Cochin
Abstract : 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.
Keywords : phagocytosis resolution of inflammation Macrophage AMPK skeletal muscle regeneration
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Article dans une revue
Cell Metab, 2013, 18 (2), pp.251-64. 〈10.1016/j.cmet.2013.06.017〉
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https://www.hal.inserm.fr/inserm-00857933
Contributeur : Benedicte Chazaud <>
Soumis le : mardi 18 septembre 2018 - 21:58:07
Dernière modification le : vendredi 15 février 2019 - 13:58:09

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Rémi Mounier, Marine Théret, Ludovic Arnold, Sylvain Cuvellier, Laurent Bultot, et al.. AMPKα1 Regulates Macrophage Skewing at the Time of Resolution of Inflammation during Skeletal Muscle Regeneration.: AMPKα1 regulates macrophage skewing. Cell Metab, 2013, 18 (2), pp.251-64. 〈10.1016/j.cmet.2013.06.017〉. 〈inserm-00857933v2〉

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