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Scheler, M. ; Irmler, M. ; Lehr, S. ; Hartwig, S. ; Staiger, H. ; Al-Hasani, H. ; Beckers, J. ; Hrabě de Angelis, M. ; Häring, H.-U. ; Weigert, C.

Cytokine response of primary human myotubes in an in vitro exercise model.

Am. J. Physiol.-Cell Physiol. 305, C877-C886 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Muscle contraction during exercise is a major stimulus for the release of peptides and proteins (myokines) that are supposed to take part in the beneficial adaptation to exercise. We hypothesize that application of an in vitro exercise stimulus as electric pulse stimulation (EPS) to human myotubes enables the investigation of the molecular response to exercise in a clearly defined model. We applied EPS for 24 h to primary human myotubes and studied the whole genome-wide transcriptional response as well as the release of candidate myokines. We observed 183 differentially regulated transcripts with fold changes >1.3. The transcriptional response resembles several properties of the in vivo situation in the skeletal muscle after endurance exercise, namely significant enrichment of pathways associated with interleukin and chemokine signaling, lipid metabolism, and antioxidant defense. Multiplex immunoassays verified the translation of the transcriptional response of several cytokines into high-secretion levels (IL-6, IL-8, CXCL1, LIF, CSF3, IL-1B, and TNF) and the increased secretion of further myokines such as angiopoietin-like 4. Notably, EPS did not induce the release of creatine kinase. Inhibitor studies and immunoblotting revealed the participation of ERK1/2-, JNK-, and NF-κB-dependent pathways in the upregulation of myokines. To conclude, our data highlight the importance of skeletal muscle cells as endocrine cells. This in vitro exercise model is not only suitable to identify exercise-regulated myokines, but it might be applied to primary human myotubes obtained from different muscle biopsy donors to study the molecular mechanisms of the individual response to exercise.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Myokine ; Electric Pulse Stimulation ; Il-8 ; Angptl4 ; Erk ; Human Myotubes; Human Skeletal-muscle ; Nf-kappa-b ; Activated Protein-kinase ; Eccentric Exercise ; Gene-expression ; C2c12 Myotubes ; Fat Oxidation ; Messenger-rna ; Stat3 Pathway ; Cross-talk
ISSN (print) / ISBN 0363-6143
e-ISSN 1522-1563
Journal American Journal of Physiology - Cell Physiology
Quellenangaben Volume: 305, Issue: 8, Pages: C877-C886 Article Number: , Supplement: ,
Publisher American Physiological Society
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Institute of Diabetes Research and Metabolic Diseases (IDM)