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Cited by 123Exercise and Physiological ResponsesMuscle Physiology and DisordersCardiovascular and exercise physiology

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

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Scheler, Mika, Irmler, Martin, Lehr, Stefan, Hartwig, Sonja, Staiger, Harald, Al-Hasani, Hadi, Beckers, Johannes, Hrabé de Angelis, Martin +2 more·2013·American Journal of Physiology-Cell Physiology
DOI 10.1152/ajpcell.00043.2013
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Abstract

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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Crossref · 10.1152/ajpcell.00043.2013

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  • When muscle contraction was stimulated in myocytes during exercise using electrical pulse stimulus, ANGPTL4 gene expression increased after 4 h and supernatant proteins increased after 8 h of stimulation.

    “It was seen that when muscle contraction was stimulated in myocytes during exercise using electrical pulse stimulus, there was an increase in the gene expression of ANGPTL4 after 4 h, and an increase of the supernatant proteins after 8 h of stimulation, corroborating the link between exercise and the expression of ANGPTL4 (Scheler et al., 2013).”

    From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Scheler et al., 2013

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Authors
Scheler, M., Irmler, M., Lehr, S., Hartwig, S., Staiger, H., Al-Hasani, H., Beckers, J., Hrabé de Angelis, M., Häring, H.-U., & Weigert, C.
Affiliations
  • Helmholtz Munich (DE)
  • Deutsches Diabetes-Zentrum e.V. (DE)
  • Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Duesseldorf, Germany;
  • Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany;
Corresponding author
Weigert, Cora
ORCID
Venue
American Journal of Physiology-Cell Physiology
Publisher
American Physiological Society
Published
2013-10-15
Volume
305
Issue
8
Pages
C877-C886
ISSN
  • 0363-6143 (ISSN-L)
  • 1522-1563
DOI
10.1152/ajpcell.00043.2013
OpenAlex
W2124102100
Cited by
123
References
49
Citations by year
2026: 5 · 2025: 2 · 2024: 10 · 2023: 8 · 2022: 9 · 2021: 14 · 2020: 8 · 2019: 11 · 2018: 9 · 2017: 15 · 2016: 11 · 2015: 16 · 2014: 4 · 2013: 1
FWCI
11.39
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • American Journal of Physiology-Cell Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
  • Site cant be reached (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft
  • Bundesministerium für Bildung und Forschung
Topics
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords
myokines, physical activity, human myotubes, electric pulse stimulation, skeletal muscle endocrine function, cytokine production, gene expression profiling, interleukin signaling, chemokine signaling, lipid metabolism, antioxidant defense, ANGPTL4, creatine kinase, ERK signaling, JNK signaling, NF-κB signaling
MeSH terms
Angiopoietin-Like Protein 4, Adult, Cells, Cultured, Colony-Stimulating Factors, Electric Stimulation, Female, Humans, Male, Muscle Contraction, Tumor Necrosis Factor-alpha, Exercise, Interleukin-6, Cytokines, Interleukin-8, NF-kappa B, Muscle, Skeletal, Muscle Fibers, Skeletal, Angiopoietins, JNK Mitogen-Activated Protein Kinases, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation, Interleukin-1beta, Leukemia Inhibitory Factor, Chemokine CXCL1

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