IL-6 release from muscles during exercise is stimulated by lactate-dependent protease activity
| Autor: | Mette Marie Åbom, Thomas Krag, Britt Lauenborg, Christine Dethlefsen, Nynne Nørgaard-Christensen, Bente Klarlund Pedersen, Pernille Hojman, Julie Gehl, Camilla Brolin, Cecilie K. Olsen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Chemokine CXCL1 Interleukin-1beta Muscle Fibers Skeletal Physical activity 03 medical and health sciences Mice Young Adult 0302 clinical medicine Physiology (medical) Internal medicine Physical Conditioning Animal Myokine medicine Animals Humans Lactic Acid Interleukin 6 Muscle Skeletal Exercise Metalloproteinase Protease biology Chemistry Interleukin-6 Tumor Necrosis Factor-alpha Electric Stimulation Interleukin-10 030104 developmental biology Endocrinology Matrix Metalloproteinase 9 biology.protein Cytokines Matrix Metalloproteinase 2 030217 neurology & neurosurgery |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 316(5) |
| ISSN: | 1522-1555 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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