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IL-6 release from muscles during exercise is stimulated by lactate-dependent protease activity.
Hojman, Pernille; Brolin, Camilla; Nørgaard-Christensen, Nynne; Dethlefsen, Christine; Lauenborg, Britt; Olsen, Cecilie Køllner; Åbom, Mette Marie; Krag, Thomas; Gehl, Julie; Pedersen, Bente Klarlund.
Afiliación
  • Hojman P; Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Copenhagen University Hospital, University of Copenhagen , Copenhagen , Denmark.
  • Brolin C; Department of Cellular and Molecular Medicine, University of Copenhagen , Copenhagen , Denmark.
  • Nørgaard-Christensen N; Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Copenhagen University Hospital, University of Copenhagen , Copenhagen , Denmark.
  • Dethlefsen C; Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Copenhagen University Hospital, University of Copenhagen , Copenhagen , Denmark.
  • Lauenborg B; Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Copenhagen University Hospital, University of Copenhagen , Copenhagen , Denmark.
  • Olsen CK; Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Copenhagen University Hospital, University of Copenhagen , Copenhagen , Denmark.
  • Åbom MM; Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Copenhagen University Hospital, University of Copenhagen , Copenhagen , Denmark.
  • Krag T; Copenhagen Neuromuscular Center, Copenhagen University Hospital, University of Copenhagen , Copenhagen , Denmark.
  • Gehl J; Center for Experimental Drug and Gene Electrotransfer, Department of Oncology and Palliative Care, Zealand University Hospital , Roskilde , Denmark.
  • Pedersen BK; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark.
Am J Physiol Endocrinol Metab ; 316(5): E940-E947, 2019 05 01.
Article en En | MEDLINE | ID: mdl-30779630
IL-6 is secreted from muscles to the circulation during high-intensity and long-duration exercise, where muscle-derived IL-6 works as an energy sensor to increase release of energy substrates from liver and adipose tissues. We investigated the mechanism involved in the exercise-mediated surge in IL-6 during exercise. Using interval-based cycling in healthy young men, swimming exercise in mice, and electrical stimulation of primary human muscle cells, we explored the role of lactate production in muscular IL-6 release during exercise. First, we observed a tight correlation between lactate production and IL-6 release during both strenuous bicycling and electrically stimulated muscle cell cultures. In mice, intramuscular injection of lactate mimicked the exercise-dependent release of IL-6, and pH buffering of lactate production during exercise attenuated IL-6 secretion. Next, we used in vivo bioimaging to demonstrate that intrinsic intramuscular proteases were activated in mice during swimming, and that blockade of protease activity blunted swimming-induced IL-6 release in mice. Last, intramuscular injection of the protease hyaluronidase resulted in dramatic increases in serum IL-6 in mice, and immunohistochemical analyses showed that intramuscular lactate and hyaluronidase injections led to release of IL-6-containing intramyocellular vesicles. We identified a pool of IL-6 located within vesicles of skeletal muscle fibers, which could be readily secreted upon protease activity. This protease-dependent release of IL-6 was initiated by lactate production, linking training intensity and lactate production to IL-6 release during strenuous exercise.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-6 / Músculo Esquelético / Fibras Musculares Esqueléticas / Ácido Láctico / Metaloproteinasa 2 de la Matriz / Metaloproteinasa 9 de la Matriz Tipo de estudio: Prognostic_studies Límite: Adult / Animals / Humans / Male Idioma: En Revista: Am J Physiol Endocrinol Metab Asunto de la revista: ENDOCRINOLOGIA / FISIOLOGIA / METABOLISMO Año: 2019 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-6 / Músculo Esquelético / Fibras Musculares Esqueléticas / Ácido Láctico / Metaloproteinasa 2 de la Matriz / Metaloproteinasa 9 de la Matriz Tipo de estudio: Prognostic_studies Límite: Adult / Animals / Humans / Male Idioma: En Revista: Am J Physiol Endocrinol Metab Asunto de la revista: ENDOCRINOLOGIA / FISIOLOGIA / METABOLISMO Año: 2019 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos