title: Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice.
abstract: Duchenne muscular dystrophy (DMD) is characterized by progressive lethal muscle degeneration and chronic inflammatory response. The mdx mouse strain has served as the animal model for human DMD. However, while DMD patients undergo extensive necrosis, the affected muscles of adult mdx mice rapidly regenerates and regains structural and functional integrity. The basis for the mild effects observed in mice compared with the lethal consequences in humans remains unknown. In this study, we provide evidence that interleukin-6 (IL-6) is causally linked to the pathogenesis of muscular dystrophy. We report that forced expression of IL-6, in the adult mdx mice, recapitulates the severe phenotypic characteristics of DMD in humans. Increased levels of IL-6 exacerbate the dystrophic muscle phenotype, sustaining inflammatory response and repeated cycles of muscle degeneration and regeneration, leading to exhaustion of satellite cells. The mdx/IL6 mouse closely approximates the human disease and more faithfully recapitulates the disease progression in humans. This study promises to significantly advance our understanding of the pathogenic mechanisms that lead to DMD.
authors.affiliation: Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM and.
authors.forename: Laura
authors.initials: L
authors.lastname: Pelosi
authors.affiliation: Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM and.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Berardinelli
authors.affiliation: Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM and.
authors.forename: Laura
authors.initials: L
authors.lastname: Forcina
authors.affiliation: Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM and.
authors.forename: Elisa
authors.initials: E
authors.lastname: Spelta
authors.affiliation: Department of Mechanical and Aerospace Engineering, Sapienza University of Rome, Rome 00184, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Rizzuto
authors.affiliation: Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM and.
authors.forename: Carmine
authors.initials: C
authors.lastname: Nicoletti
authors.affiliation: Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM and.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Camilli
authors.affiliation: Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM and.
authors.forename: Erika
authors.initials: E
authors.lastname: Testa
authors.affiliation: DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Rome 00161, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Catizone
authors.affiliation: Division of Rheumatology, Bambino Gesù Children's Hospital, Rome 00100, Italy and.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Benedetti
authors.affiliation: Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM and Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome 00161, Italy antonio.musaro@uniroma1.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Musarò
mesh_terms: D000818:Animals; D015536:Down-Regulation; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018101:Mice, Inbred mdx; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000473:pathology; D013234:Stem Cells / Q000473:pathology; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D015850:Interleukin-6; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase; C577686:interleukin-6, mouse