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IL-7 is expressed and secreted by human skeletal muscle cells
Abstract
In addition to generating movement, skeletal muscle may have a function as a secretory organ. The aim of the present study was to identify novel proteins with signaling capabilities secreted from skeletal muscle cells. IL-7 was detected in media conditioned by primary cultures of human myotubes differentiated from satellite cells, and concentrations increased with incubation time. By immunoblotting and real-time RT-PCR IL-7 expression was confirmed at both protein and mRNA levels. Furthermore, with immunofluorescence and specific antisera, multinucleated myotubes were found to coexpress IL-7 and myosin heavy chain. During differentiation of human myotubes from satellite cells, IL-7 expression increased at mRNA and protein levels. In contrast, mRNA expression of the IL-7 receptor was 80% lower in myotubes compared with satellite cells. Incubations with recombinant IL-7 under differentiation conditions caused approximately 35% reduction in mRNA for the terminal myogenic markers myosin heavy chain 2 (MYH2) and myogenin (MYOG), suggesting that IL-7 may act on satellite cells to inhibit development of the muscle fiber phenotype. Alternative routes of cell development were investigated, and IL-7 increased migration of satellite cells by 40% after 48 h in a Transwell system, whereas cell proliferation remained unchanged. In vivo, real-time RT-PCR analysis of musculus vastus lateralis (n = 10) and musculus trapezius (n = 7) biopsies taken from male individuals undergoing a strength training program demonstrated that after 11 wk mean IL-7 mRNA increased by threefold (P = 0.01) and fourfold (P = 0.04), respectively. In conclusion, we have demonstrated that IL-7 is a novel myokine regulated both in vitro and in vivo, and it may play a role in the regulation of muscle cell development.
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“A number of other myokines, including IL‑15 (53) and IL-7 (54) have further been demonstrated to possess anabolic features in rodent models.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [54]
In the citing paper
“A post-exercise surge in thymopoiesis is possible considering that skeletal muscle secretes IL-7 (Haugen et al. 2010) which might in turn increase thymic mass and lead to the emergence of recent thymic emigrants (Fry and Mackall 2005).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Haugen et al. 2010
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“IL-7 (22), IL-15 (23), leukemia inhibitory factor (LIF) (24), and”
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Ibeas, K., Herrero, L., Mera, P., & Serra, D. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114640 · Cited by 39
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“Gene expression was detected by qRT-PCR, and myogenin and myosin heavy chain isoforms MYH2 and MYH7 were used as differentiation markers (Asp et al. 2009; Haugen et al. 2010).”
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BackgroundMathematical Model of Naive T Cell Division and Survival IL-7 Thresholds
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“IL-7 functions as a myokine in nonimmune cells (Haugen et al., 2010).”
BackgroundRenin-angiotensin system in mammalian kidney development
Yosypiv, I. V. (2020) · Pediatric Nephrology · doi:10.1007/s00467-020-04496-5 · Cited by 23
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Diverse Interleukin-7 mRNA Transcripts in Chinese Tree Shrew (Tupaia belangeri chinensis)
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“Besides its pleiotropic role in the immune system, IL7 has been reported as a regulator of the development of central nervous system [13] and myogenesis and skeletal muscle cell migration [14].”
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“IL-7 is another myokine that is secreted by skeletal muscle as a key regulator of B- and Tcells differentiation (Ceredig & Rolink, 2012; Haugen et al., 2010).”
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“IL-7 has been found to reduce myoblast differentiation and fusion 50 , so future studies measuring whether increased IL-7 induced by critical VML upregulates CD127 + T cells and impedes myogenesis is of interest.”
Associations of Serum CXCL12α and CK Levels with Skeletal Muscle Mass in Older Adults
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“Furthermore, CK levels were positively associated with serum levels of IL-7 and CCL3 (Figure 1c,d), which have been previously implicated in the regulation of human skeletal muscle stem cells and muscle tissue regeneration [39,40].”
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“However, considering the importance of T cells in clearing viral infections, exercise may stimulate the production of naive T cells, as previous studies determined that contracting skeletal muscle produces IL-7 [47], which may increase thymic mass and function [48].”
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“IL-7 mRNA expression is upregulated in human skeletal muscle following resistance training with some evidence that it may increase myoblast migration toward myotube formation [38], and act on satellite cells [68].”
BackgroundInfluentialSecretome Analysis of Skeletal Myogenesis Using SILAC and Shotgun Proteomics
Chan, C. Y. X., McDermott, J. C., & Siu, K. W. M. (2011) · International Journal of Proteomics · doi:10.1155/2011/329467 · Cited by 15
“Apart from the well-known myokines, such as members of the insulin-like growth factor1 (IGF1) [81–90] and transforming growth factor (TGF) families [91–99], which have potent, but opposing effects on myogenesis, there were individual studies investigating other myokines, such as plasminogen activator [100], collagenas…”
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“IL-7, mostly produced in the thymus, is expressed and secreted by human skeletal muscle cells as well; it is classified as an exercise-regulated myokine, and exercise can restore IL-7 decline induced by aging [79,88].”
BackgroundMyokines: Do they really exist?
Manabe, Y., Miyatake, S., & Takagi, M. (2012) · The Journal of Physical Fitness and Sports Medicine · doi:10.7600/jpfsm.1.51 · Cited by 11
Mechanisms Underlying the Rarity of Skeletal Muscle Cancers
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“Strength training increased the expression of IL-7 mRNA in resting SKM [213]; IL-7 expression also increased following a single soccer match [214].”
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“66 This myokine is also a potential regulator of osteoclastogenesis and bone resorption both via a receptor activator of nuclear factor kappa ‐ β ligand (RANKL) ‐ dependent and RANKL ‐ independent pathways.”
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“During skeletal muscle exercise, IL-15 and IL-7 are highly expressed and secreted, playing a role in maintaining T cell homeostasis [93,94].”
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“IL-7 might affect satellite cells during muscle development, and is secreted and expressed by human skeletal muscle cells [72,73].”
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Powers, S. K., Goldstein, E. R., Lategan-Potgieter, R., Schrager, M. A., Skelton, M., & Demirel, H. A. (2025) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2025.02.010 · Cited by 7
“152 IL-7 is hypothesized to contribute to muscle hypertrophy by promotion of myoblast migration and differentiation.”
Белкина, Т. В., Averina, O. V., Savenkova, E. V., & Даниленко, В. Н. (2021) · Biology Bulletin Reviews · doi:10.1134/s2079086421040034 · Cited by 7
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“178,179 Brain-derived neurotrophic factor (BDNF) is a myo-kine that positively regulates myogenesis via enhancing AMPK activity.”
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“For example, platelet-derived growth factor subunit B (PDGFB) and IL7 are both myokines with potential effects on muscle differentiation ( Haugen et al., 2010 ; Hamaguchi et al., 2023 ).”
BackgroundCharacteristics of Skeletal Muscle as a Secretory Organ
Aoi, W. (2017) · Springer eBooks · doi:10.1007/978-981-10-3292-9_9 · Cited by 5
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Bortolini, M. J. S., da Silva, M. V., Alonso, F. M., de Medeiros, L. A., Carvalho, F. R., Costa, L. F., Silva, N. M., Penha‐Silva, N., Mineo, T. W. P., & Mineo, J. R. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00641 · Cited by 4
“IL-15 can also be produced by muscle in vitro (Grabstein et al., 1994) or after strength exercise in humans (Nielsen et al., 2007), as well IL-7 (Haugen et al., 2010).”
BackgroundInfluentialMyokines: A potential key factor in development, treatment, and biomarker of sarcopenia
Aoi, W. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822146-4.00006-5 · Cited by 4
Establishing Predictors of Acute Sarcopenia: A Proof-Of-Concept Study Utilising Network Analysis
Welch, C., Bravo, L., Gkoutos, G. V., Greig, C. A., Lewis, D., Lord, J. M., Majid, Z., Masud, T., McGee, K. C., Moorey, H. C., et al. (2024) · Aging and Disease · doi:10.14336/ad.2024.0167 · Cited by 4
“IL-7 is expressed and secreted by human skeletal muscle cells [28].”
Pedersen, B. K. (2016) · Springer eBooks · doi:10.1007/978-3-319-11251-0_31 · Cited by 4
Acheson, J., Joanisse, S., Sale, C., & Hodson, N. W. (2024) · Bioscience Reports · doi:10.1042/bsr20240137 · Cited by 4
Exercise-secreted antitumor myokines: mechanistic insights and translational potential
Han, S., Du, C., Zhao, C., Zhang, Q., Wu, M., Yang, C., & Liu, X. (2026) · Frontiers in Sports and Active Living · doi:10.3389/fspor.2026.1830759 · Cited by 3
“IL-7 and IL-15 are key regulators of T cell homeostasis, and their secretion by skeletal muscle increases markedly after exercise (53).”
Anti-inflammatory Effects of Probiotics and Their Metabolites: Possible Role for Epigenetic Effects
Türker, N., Toh, Z. Q., Karagiannis, T. C., & Licciardi, P. V. (2014) · Springer eBooks · doi:10.1007/978-1-4939-0706-9_5 · Cited by 4
Regenerative Effects of Hypoxia Primed Flowable Placental Formulation in Muscle and Dermal Injury
Dhall, S., Park, M. S., Li, C., & Sathyamoorthy, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137151 · Cited by 2
Revascularization and muscle adaptation to limb demand ischemia in diet-induced obese mice
Albadawi, H., Tzika, A. A., Rask‐Madsen, C., Crowley, L. M., Koulopoulos, M. W., Yoo, H., & Watkins, M. T. (2016) · Journal of Surgical Research · doi:10.1016/j.jss.2016.06.001 · Cited by 3
“Higher IL-7 gene expression and plasma levels were reported after exercise and suggested to play a role in myogenesis.(33)”
BackgroundLifestyle Interventions to Improve Immunesenescence
Bartlett, D. B., & Huffman, K. M. (2016) · Springer eBooks · doi:10.1007/978-3-319-43365-3_10 · Cited by 3
Global multi-omics analysis of exerkines in progressive treadmill-exercised rodentsPreprint
Taha, H. B. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.08.627439 · Cited by 3
Erythrocytes as a Source of Exerkines
Misiti, F., Falese, L., Iannaccone, A., & Diotaiuti, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199665 · Cited by 2
“In addition, a range of other exerkines are recognized, including IL7 [8], 12,13-diHOME [9], myonectin [10], myostatin [11], METRNL, CSF1, decorin [12–15], SFRP4 [5], fetuin-A [16], and ANGPTL4 [17], among many others [5].”
Muscle–immune metabolic crosstalk: shared pathways in cachexia and exercise
Westermann, S., Bennühr, B., Fumo, A. R., Rohm, M., & Hiller, K. (2026) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2026.103455 · Cited by 2
Baseggio, L., Wissmann, I. B., Coelho, R. C. D., & Cardoso, A. M. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.112006 · Cited by 2
Aoi, W. (2013) · 体力科學 · doi:10.7600/jspfsm.62.263 · Cited by 2
Cross-Platform Transcriptomic Analysis of 40 Human and Rodent Skeletal Muscle Exerkines
Taha, H. B., Robbins, N., Zoha, F.-S., Zhu, S., Vivek, N., & Bogoniewski, A. (2026) · Muscles · doi:10.3390/muscles5010015 · Cited by 1
“…in inflammatory signaling that is often discussed as an exerkine, with proposed roles during physical activity in shaping inflammatory responses and supporting muscle repair and recovery, although its exercise responsiveness across humans and rodents remains an active area of investigation [67,68].”
Two‐Way Communication Between Skeletal Muscle and Myokines
Huang, T., Zhou, S., Chen, X., Chen, D., Yu, B., & Huang, Z. (2026) · Cell Biochemistry and Function · doi:10.1002/cbf.70267 · Cited by 1
“Haugen and co‐workers found that IL‐7 improved satellite cell migration and reduced differentiation, but did not affect satellite cell proliferation, which led them to hypothesize that IL‐7 would enhance satellite cell migration at the expense of differentiation [43].”
Role of myokines in regulation of a power exchange
Scherbakov, V. I., Александровна, С. Г., & Ryabichenko, T. I. (2012) · Bulletin of Siberian Medicine · doi:10.20538/1682-0363-2012-3-173-178 · Cited by 1
Osteoimmunological Aspects of Biomechanics
Kerschan‐Schindl, K., & EBENBICHLER, G. R. (2011) · Springer eBooks · doi:10.1007/978-3-7091-0520-7_5 · Cited by 1
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Mavoungou, L. O., Neuenschwander, S., Pham, U., Iyer, P. S., & Mermod, N. (2019) · Stem Cell Research · doi:10.1016/j.scr.2019.101619 · Cited by 1
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Exercise on cytokine responses in males and females: Effect of leucine, HMB and BCAAPreprint
Brown, A. D., Γραμμένου, Μ., Tee, C. C. L., Chong, M. C., & Stewart, C. E. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.11.548561 · Cited by 1
“Furthermore, Haugen et al. (2010) reported that IL-7 is produced by primary muscle myotubes and is reported to activate T-cells which are important during the inflammatory process.”
BackgroundLee-Ødegård, S., Hjorth, M., Olsén, T., Moen, G.-H., Daubney, E. R., Evans, D. M., Hevener, A. L., Lusis, A. J., Zhou, M., Seldin, M. M., et al. (2024) · medRxiv · doi:10.1101/2024.02.10.24302626 · Cited by 1
“For example, platelet-derived growth factor subunit B (PDGFB) and IL7, are both myokines with potential effects on muscle differentiation 15,31 .”
BackgroundLee-Ødegård, S., Hjorth, M., Olsén, T., Moen, G.-H., Daubney, E. R., Evans, D. M., Hevener, A. L., Lusis, A. J., Zhou, M., Seldin, M. M., et al. (2024) · eLife · doi:10.7554/elife.96535.1 · Cited by 1
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Spielmann, G. (2026) · Edinburgh Napier Research Repository (Edinburgh Napier University) · doi:10.17869/enu.192070
Metadata
- Authors
- Haugen, F., Norheim, F., Lian, H., Wensaas, A. J., Dueland, S., Berg, O., Funderud, A., Skålhegg, B. S., Raastad, T., & Drevon, C. A.
- Affiliations
- University of Oslo (NO)
- Norwegian School of Sport Sciences (NO)
- Corresponding author
- Haugen, Fred
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2010-04
- Volume
- 298
- Issue
- 4
- Pages
- C807-C816
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2112164340
- Cited by
- 237
- References
- 50
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 24 · 2023: 14 · 2022: 14 · 2021: 17 · 2020: 20 · 2019: 11 · 2018: 9 · 2017: 7 · 2016: 18 · 2015: 18 · 2014: 8 · 2013: 15 · 2012: 18
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- IL-7, myokines, skeletal muscle, satellite cells, myotubes, myogenesis, IL-7 receptor, myosin heavy chain, myogenin, resistance training, vastus lateralis, trapezius, muscle fiber phenotype
- MeSH terms
- Adult, Cell Differentiation, Cells, Cultured, Culture Media, Humans, Male, Middle Aged, RNA, Messenger, Biomarkers, Interleukin-7, Muscle Fibers, Skeletal, Myosin Heavy Chains, Receptors, Interleukin-7, Muscle Development, Satellite Cells, Skeletal Muscle, Cell Proliferation, Resistance Training
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