IL-15 promotes human myogenesis and mitigates the detrimental effects of TNF alpha on myotube development
dc.contributor.author | O'Leary, MF | |
dc.contributor.author | Wallace, GR | |
dc.contributor.author | Bennett, AJ | |
dc.contributor.author | Tsintzas, K | |
dc.contributor.author | Jones, SW | |
dc.date.accessioned | 2019-03-06T09:39:58Z | |
dc.date.issued | 2017-10-11 | |
dc.description.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. | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.identifier.citation | Vol. 7, 12997 | en_GB |
dc.identifier.doi | 10.1038/s41598-017-13479-w | |
dc.identifier.uri | http://hdl.handle.net/10871/36307 | |
dc.language.iso | en | en_GB |
dc.publisher | Nature Research | en_GB |
dc.rights | © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | en_GB |
dc.subject | ageing | en_GB |
dc.subject | muscle stem cells | en_GB |
dc.title | IL-15 promotes human myogenesis and mitigates the detrimental effects of TNF alpha on myotube development | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-03-06T09:39:58Z | |
dc.identifier.issn | 2045-2322 | |
exeter.article-number | ARTN 12997 | en_GB |
dc.description | This is the final version. Available from Nature Research via the DOI in this record. | en_GB |
dc.identifier.journal | Scientific Reports | en_GB |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2017-09-26 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2017-09-26 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-03-06T09:36:50Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2019-03-06T09:40:00Z | |
refterms.panel | C | en_GB |
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Except where otherwise noted, this item's licence is described as © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.