IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development

O’Leary, Mary F. and Wallace, Graham R. and Bennett, Andrew J. and Tsintzas, Kostas and Jones, Simon W. (2017) IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development. Scientific Reports, 7 (1). 12997/1-12997/11. ISSN 2045-2322

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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.

Item Type: Article
Keywords: Ageing; Muscle stem cells
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: 10.1038/s41598-017-13479-w
Depositing User: Eprints, Support
Date Deposited: 05 Apr 2018 11:45
Last Modified: 05 Apr 2018 13:18
URI: http://eprints.nottingham.ac.uk/id/eprint/50963

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