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 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.

Protein-carbohydrate ingestion alters Vps34 cellular localization independent of changes in kinase activity in human skeletal muscle

“…Human primary myoblasts were isolated from 4 patients (age 61±6yrs, BMI 28.7±0.65kg/m 2 , mean±SEM) as previously described (23). Cells were passaged at 60% confluency on 0.2% gelatin-coated 100mm culture plates in Hams F10 media (ThermoFisher Scientific, supplemented with 20% FBS and 1% PS) to prevent spontaneous fusion of myoblasts to myotubes, and at passage 3 were seeded onto 6-well plates at a density of 5×10 4 cells/well.…”

Obese subcutaneous adipose tissue impairs human myogenesis, particularly in old skeletal muscle, via resistin-mediated activation of NFκB

“…The study was approved by the University of Nottingham Medical School Ethics Committee (G11092014SoLS) and was conducted in accordance with the guidelines of the Declaration of Helsinki. A vastus lateralis muscle biopsy was obtained from each subject and the satellite cell population extracted as previously described 32 . Our isolation technique has consistently generated cultures in our laboratories that produce desmin positive multinucleated myotubes that are negative for the fibroblast marker TE7 32 .…”

“…A vastus lateralis muscle biopsy was obtained from each subject and the satellite cell population extracted as previously described 32 . Our isolation technique has consistently generated cultures in our laboratories that produce desmin positive multinucleated myotubes that are negative for the fibroblast marker TE7 32 . Additionally, commercially available primary human myoblasts (Thermo Fisher cat.…”

Serum Interleukin-15 and its relationship with adiposity Indices before and after short-term endurance exercise

“…First discovered in 1994 as an immune modulating agent, 1 it is considered anabolic for proteins, enhancing myogenesis and providing protection against protein degradation. 2 The release of IL-15 upon exercise also increases glucose uptake by translocating GLUT4 to the plasma membrane. 3 Due to its anabolic and muscle building effects, it has also been called as the ‘Arnold cytokine’ after the body builder Arnold Schwartzenneger.…”