| Autor: |
Markworth JF; Department of Molecular & Integrative Physiology.; Department of Orthopaedic Surgery., Brown LA; Department of Molecular & Integrative Physiology., Lim E; Department of Molecular & Integrative Physiology., Floyd C; Department of Molecular & Integrative Physiology., Larouche J; Department of Biomedical Engineering, and., Castor-Macias JA; Department of Biomedical Engineering, and., Sugg KB; Department of Orthopaedic Surgery.; Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA., Sarver DC; Department of Orthopaedic Surgery.; Department of Cellular & Molecular Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Macpherson PC; Department of Molecular & Integrative Physiology., Davis C; Department of Molecular & Integrative Physiology., Aguilar CA; Department of Biomedical Engineering, and., Maddipati KR; Department of Pathology, Lipidomics Core Facility, Wayne State University, Detroit, Michigan, USA., Brooks SV; Department of Molecular & Integrative Physiology.; Department of Biomedical Engineering, and. |
| Abstrakt: |
Specialized proresolving mediators (SPMs) actively limit inflammation and expedite its resolution by modulating leukocyte recruitment and function. Here we profiled intramuscular lipid mediators via liquid chromatography-tandem mass spectrometry-based metabolipidomics following myofiber injury and investigated the potential role of SPMs in skeletal muscle inflammation and repair. Both proinflammatory eicosanoids and SPMs increased following myofiber damage induced by either intramuscular injection of barium chloride or synergist ablation-induced functional muscle overload. Daily systemic administration of the SPM resolvin D1 (RvD1) as an immunoresolvent limited the degree and duration of inflammation, enhanced regenerating myofiber growth, and improved recovery of muscle strength. RvD1 suppressed inflammatory cytokine expression, enhanced polymorphonuclear cell clearance, modulated the local muscle stem cell response, and polarized intramuscular macrophages to a more proregenerative subset. RvD1 had minimal direct impact on in vitro myogenesis but directly suppressed myokine production and stimulated macrophage phagocytosis, showing that SPMs can modulate both infiltrating myeloid and resident muscle cell populations. These data reveal the efficacy of immunoresolvents as a novel alternative to classical antiinflammatory interventions in the management of muscle injuries to modulate inflammation while stimulating tissue repair. |
