Mary F. O�Leary
IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development
O�Leary, Mary F.; Wallace, Graham R.; Bennett, Andrew J.; Tsintzas, Kostas; Jones, Simon W.
Authors
Graham R. Wallace
Dr ANDREW BENNETT ANDREW.BENNETT@NOTTINGHAM.AC.UK
ASSOCIATE PROFESSOR
Professor KOSTAS TSINTZAS kostas.tsintzas@nottingham.ac.uk
PROFESSOR OF HUMAN PHYSIOLOGY
Simon W. Jones
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.
Citation
O’Leary, M. F., Wallace, G. R., Bennett, A. J., Tsintzas, K., & Jones, S. W. (in press). IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development. Scientific Reports, 7(1), Article 12997. https://doi.org/10.1038/s41598-017-13479-w
Journal Article Type | Article |
---|---|
Acceptance Date | Sep 26, 2017 |
Online Publication Date | Oct 11, 2017 |
Deposit Date | Apr 5, 2018 |
Publicly Available Date | Apr 5, 2018 |
Journal | Scientific Reports |
Electronic ISSN | 2045-2322 |
Publisher | Nature Publishing Group |
Peer Reviewed | Peer Reviewed |
Volume | 7 |
Issue | 1 |
Article Number | 12997 |
DOI | https://doi.org/10.1038/s41598-017-13479-w |
Keywords | Ageing; Muscle stem cells |
Public URL | https://nottingham-repository.worktribe.com/output/887224 |
Publisher URL | https://www.nature.com/articles/s41598-017-13479-w |
Contract Date | Apr 5, 2018 |
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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