1. AMPKα1 Regulates Macrophage Skewing at the Time of Resolution of Inflammation during Skeletal Muscle Regeneration.: AMPKα1 regulates macrophage skewing
- Author
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Kei Sakamoto, Bénédicte Chazaud, Marine Theret, Benoit Viollet, Ludovic Arnold, Rémi Mounier, Olga Göransson, Laurent Bultot, Marc Foretz, Sylvain Cuvellier, Arnaud Ferry, Nieves Sanz, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Department of Experimental Medical Sciences [Lund, Sweden], Lund University [Lund], Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Nutrition, Nestlé Institute of Health Sciences SA, Department of Experimental Medical Sciences, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Association française contre les myopathies ( AFM-Téléthon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC)
- Subjects
Male ,AMPK ,Physiology ,Macrophage ,Phagocytosis ,Cell ,Inflammation ,Apoptosis ,Calcium-Calmodulin-Dependent Protein Kinase Kinase ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,AMP-Activated Protein Kinases ,Proinflammatory cytokine ,03 medical and health sciences ,Mice ,0302 clinical medicine ,skeletal muscle regeneration ,medicine ,Leukocytes ,Animals ,Regeneration ,Muscle, Skeletal ,Molecular Biology ,Cells, Cultured ,030304 developmental biology ,Mice, Knockout ,resolution of inflammation ,0303 health sciences ,[ SDV.BC ] Life Sciences [q-bio]/Cellular Biology ,Macrophages ,Skeletal muscle ,phagocytosis ,Cell Biology ,Macrophage Activation ,Phenotype ,Cell biology ,medicine.anatomical_structure ,medicine.symptom ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
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.
- Published
- 2013
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