title: Paracrine cross-talk between skeletal muscle and macrophages in exercise by PGC-1α-controlled BNP.
abstract: Activation of resident and infiltrating immune cells is a central event in training adaptation and other contexts of skeletal muscle repair and regeneration. A precise orchestration of inflammatory events in muscle fibers and immune cells is required after recurrent contraction-relaxation cycles. However, the mechanistic aspects of this important regulation remain largely unknown. We now demonstrate that besides a dominant role in controlling cellular metabolism, the peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) also has a profound effect on cytokine expression in muscle tissue. Muscle PGC-1α expression results in activation of tissue-resident macrophages, at least in part mediated by PGC-1α-dependent B-type natriuretic peptide (BNP) production and secretion. Positive effects of exercise in metabolic diseases and other pathologies associated with chronic inflammation could accordingly involve the PGC-1α-BNP axis and thereby provide novel targets for therapeutic approaches.
authors.affiliation: Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Regula
authors.initials: R
authors.lastname: Furrer
authors.affiliation: Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Petra S
authors.initials: PS
authors.lastname: Eisele
authors.affiliation: Biozentrum, Proteomics Core Facility, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Beer
authors.affiliation: Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Handschin
mesh_terms: D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D040901:Proteomics / Q000379:methods
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020097:Natriuretic Peptide, Brain