IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development
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 unch...
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2017
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oai:doaj.org-article:d33a33ba397f4c0e9a035dc7e4ebe3f02021-12-02T15:06:12ZIL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development10.1038/s41598-017-13479-w2045-2322https://doaj.org/article/d33a33ba397f4c0e9a035dc7e4ebe3f02017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13479-whttps://doaj.org/toc/2045-2322Abstract 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.Mary F. O’LearyGraham R. WallaceAndrew J. BennettKostas TsintzasSimon W. JonesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Mary F. O’Leary Graham R. Wallace Andrew J. Bennett Kostas Tsintzas Simon W. Jones IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development |
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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. |
format |
article |
author |
Mary F. O’Leary Graham R. Wallace Andrew J. Bennett Kostas Tsintzas Simon W. Jones |
author_facet |
Mary F. O’Leary Graham R. Wallace Andrew J. Bennett Kostas Tsintzas Simon W. Jones |
author_sort |
Mary F. O’Leary |
title |
IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development |
title_short |
IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development |
title_full |
IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development |
title_fullStr |
IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development |
title_full_unstemmed |
IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development |
title_sort |
il-15 promotes human myogenesis and mitigates the detrimental effects of tnfα on myotube development |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/d33a33ba397f4c0e9a035dc7e4ebe3f0 |
work_keys_str_mv |
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1718388543988957184 |