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Abstract
Studies in murine cell lines and in mouse models suggest that IL-15 promotes
myogenesis and may protect against the inflammation-mediated skeletal muscle
atrophy which occurs in sarcopenia and cachexia. The effects of IL-15 on human
skeletal muscle growth and development remain largely uncharacterised. Myogenic cultures were isolated from the skeletal muscle of young and elderly subjects. Myoblasts were differentiated for 8 d, with or without the addition of recombinant cytokines (rIL-15, rTNFα) and an IL-15 receptor neutralising antibody. Although myotubes were 19% thinner in cultures derived from elderly subjects, rIL-15 increased the thickness of myotubes (MTT) from both age groups to a similar extent. Neutralisation of the high-affinity IL-15 receptor binding subunit, IL-15rα in elderly myotubes confirmed that autocrine concentrations of IL-15 also support myogenesis. Co-incubation of differentiating myoblasts with rIL-15 and rTNFα, limited the reduction in MTT and nuclear fusion index (NFI) associated with rTNFα stimulation alone. IL-15rα neutralisation and rTNFα decreased MTT and NFI further. This, coupled with our observation that myotubes secrete IL-15 in response to TNFα stimulation supports the notion that IL-15 serves to mitigate inflammatory skeletal muscle loss. IL-15 may be an effective therapeutic target for the attenuation of
inflammation-mediated skeletal muscle atrophy.
myogenesis and may protect against the inflammation-mediated skeletal muscle
atrophy which occurs in sarcopenia and cachexia. The effects of IL-15 on human
skeletal muscle growth and development remain largely uncharacterised. Myogenic cultures were isolated from the skeletal muscle of young and elderly subjects. Myoblasts were differentiated for 8 d, with or without the addition of recombinant cytokines (rIL-15, rTNFα) and an IL-15 receptor neutralising antibody. Although myotubes were 19% thinner in cultures derived from elderly subjects, rIL-15 increased the thickness of myotubes (MTT) from both age groups to a similar extent. Neutralisation of the high-affinity IL-15 receptor binding subunit, IL-15rα in elderly myotubes confirmed that autocrine concentrations of IL-15 also support myogenesis. Co-incubation of differentiating myoblasts with rIL-15 and rTNFα, limited the reduction in MTT and nuclear fusion index (NFI) associated with rTNFα stimulation alone. IL-15rα neutralisation and rTNFα decreased MTT and NFI further. This, coupled with our observation that myotubes secrete IL-15 in response to TNFα stimulation supports the notion that IL-15 serves to mitigate inflammatory skeletal muscle loss. IL-15 may be an effective therapeutic target for the attenuation of
inflammation-mediated skeletal muscle atrophy.
| Original language | English |
|---|---|
| Article number | 12997 |
| Journal | Scientific Reports |
| Volume | 7 |
| DOIs | |
| Publication status | Published - 11 Oct 2017 |
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Dive into the research topics of 'IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development'. Together they form a unique fingerprint.Projects
- 1 Finished
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Centre for Musculoskeletal Ageing Research (linked to 18289 & 19482)
Lord, J. (Principal Investigator), Buckley, C. (Co-Investigator), Duda, J. (Co-Investigator), Dunn, W. (Co-Investigator), Miall, C. (Co-Investigator) & Greig, C. (Co-Investigator)
1/08/12 → 31/07/17
Project: Research Councils