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

• Published in: Scientific reports Vol. 7; no. 1; pp. 12997 - 11
• Main Authors: O’Leary, Mary F., Wallace, Graham R., Bennett, Andrew J., Tsintzas, Kostas, Jones, Simon W.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.10.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/1; 14/34; 14/63; 38/77; 631/443/7; 631/532/2439; 82/1; Aged; Aging; Animal models; Antibodies, Neutralizing - pharmacology; Atrophy; Autocrine signalling; Cachexia; Cell Differentiation - drug effects; Cell lines; Cells, Cultured; Female; Gene Expression Regulation, Developmental - drug effects; Geriatrics; Humanities and Social Sciences; Humans; Inflammation; Interleukin 15; Interleukin 15 receptors; Interleukin-15 - blood; Male; multidisciplinary; Muscle Development - drug effects; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - pathology; Musculoskeletal system; Myoblasts; Myogenesis; Myotubes; Nuclear factor I; Recombinant Proteins - pharmacology; Sarcopenia; Science; Science (multidisciplinary); Skeletal muscle; Therapeutic applications; Tumor Necrosis Factor-alpha - adverse effects; Tumor necrosis factor-α
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-13479-w

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.