Interleukin-15 receptor subunit alpha regulates interleukin-15 localization and protein expression in skeletal muscle cells.


Journal

Experimental physiology
ISSN: 1469-445X
Titre abrégé: Exp Physiol
Pays: England
ID NLM: 9002940

Informations de publication

Date de publication:
03 2022
Historique:
received: 10 11 2021
accepted: 24 01 2022
pubmed: 1 2 2022
medline: 1 4 2022
entrez: 31 1 2022
Statut: ppublish

Résumé

What is the central question of this study? How are the dynamics of interleukin (IL)-15 and its receptors altered during the differentiation of myoblasts into myotubes, and how is IL-15 regulated? What is the main finding and its importance? The mRNA levels of IL-15 and interleukin-2 receptor subunits beta and gamma increase during skeletal muscle differentiation, whereas interleukin-15 receptor subunit alpha (IL-15RA) exhibits different kinetics. IL-15RA regulates the localization and expression of IL-15 at the protein level. Interleukin-15 (IL-15) is a myokine in the interleukin-2 (IL-2) family that is generated in the skeletal muscle during exercise. The functional effect of IL-15 involves muscle regeneration and metabolic regulation in skeletal muscle. Reports have indicated that interleukin-15 receptor subunit alpha (IL-15RA) acts by regulating IL-15 localization in immune cells. However, the dynamics of IL-15 and its receptors, which regulate the IL-15 pathway in skeletal muscle differentiation, have not yet been clarified. In this study, we investigated the mechanism of IL-15 regulation using a mouse skeletal muscle cell line, C2C12 cells. We found that the mRNA expression of IL-15, interleukin-2 receptor subunit beta (IL-2RB; CD122) and interleukin-2 receptor subunit gamma (IL-2RG; CD132) increased, but that IL-15RA exhibited different kinetics as differentiation progressed. We also found that IL-15, mainly present in the cytosol, pre-assembled with IL-15RA in the cytosol and fused to the plasma membrane. Moreover, IL-15RA increased IL-15 protein levels. Our findings suggest that genes involved in the IL-15 signalling complex are enhanced with the differentiation of myotubes and that IL-15RA regulates the protein kinetics of IL-15 signalling in skeletal muscle.

Identifiants

pubmed: 35100657
doi: 10.1113/EP090205
doi:

Substances chimiques

Interleukin-15 0
Interleukin-15 Receptor alpha Subunit 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

222-232

Informations de copyright

© 2022 The Authors. Experimental Physiology © 2022 The Physiological Society.

Références

Akdis, M., Aab, A., Altunbulakli, C., Azkur, K., Costa, R. A., Crameri, R., Duan, S., Eiwegger, T., Eljaszewicz, A., Ferstl, R., Frei, R., Garbani, M., Globinska, A., Hess, L., Huitema, C., Kubo, T., Komlosi, Z., Konieczna, P., Kovacs, N., … Akdis, C. A. (2016). Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. Journal of Allergy and Clinical Immunology, 138, 984-1010. https://doi.org/10.1016/j.jaci.2016.06.033
Bamford, R. N., Grant, A. J., Burton, J. D., Peters, C., Kurys, G., Goldman, C. K., Brennan, J., Roessler, E., & Waldmann, T. A. (1994). The interleukin (IL) 2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proceedings of the National Academy of Sciences of the United States of America , 91, 4940-4944. https://doi.org/10.1073/pnas.91.11.4940
Bergamaschi, C., Rosati, M., Jalah, R., Valentin, A., Kulkarni, V., Alicea, C., Zhang, G. M., Patel, V., Felber, B. K., & Pavlakis, G. N. (2008). Intracellular interaction of interleukin-15 with its receptor α during production leads to mutual stabilization and increased bioactivity. Journal of Biological Chemistry, 283, 4189-4199. https://doi.org/10.1074/jbc.M705725200
Bernard, J., Harb, C., Mortier, E., Quéméner, A., Meloen, R. H., Vermot-Desroches, C., Wijdeness, J., van Dijken, P., Grötzinger, J., Slootstra, J. W., Plet, A., & Jacques, Y. (2004). Identification of an interleukin-15α receptor-binding site on human interleukin-15. Journal of Biological Chemistry, 279, 24313-24322. https://doi.org/10.1074/jbc.M312458200
Braun, T., & Gautel, M. (2011). Transcriptional mechanisms regulating skeletal muscle differentiation, growth and homeostasis. Nature Reviews Molecular Cell Biology, 12, 349-361. https://doi.org/10.1038/nrm3118
Briukhovetska, D., Dörr, J., Endres, S., Libby, P., Dinarello, C. A., & Kobold, S. (2021). Interleukins in cancer: From biology to therapy. Nature Reviews Cancer, 21, 481-499. https://doi.org/10.1038/s41568-021-00363-z
Burkett, P. R., Koka, R., Chien, M., Chai, S., Boone, D. L., & Ma, A. (2004). Coordinate expression and trans presentation of interleukin (IL)-15Rα and IL-15 supports natural killer cell and memory CD8+ T cell homeostasis. Journal of Experimental Medicine, 200, 825-834. https://doi.org/10.1084/jem.20041389
Cole, D. J., & Rubinstein, M. P. (2012). Soluble IL-15/IL-15Rα complexes in human serum. Blood, 120, 1-2. https://doi.org/10.1182/blood-2012-04-425306
Dubois, S., Mariner, J., Waldmann, T. A., & Tagaya, Y. (2002). IL-15Rα recycles and presents IL-15 in trans to neighboring cells. Immunity, 17, 537-547. https://doi.org/10.1016/S1074-7613(02)00429-6
Fehniger, T. A., & Caligiuri, M. A. (2001). Interleukin 15: Biology and relevance to human disease. Blood, 97, 14-32. https://doi.org/10.1182/blood.V97.1.14
Fujimoto, T., Sugimoto, K., Takahashi, T., Yasunobe, Y., Xie, K., Tanaka, M., Ohnishi, Y., Yoshida, S., Kurinami, H., Akasaka, H., Takami, Y., Takeya, Y., Yamamoto, K., & Rakugi, H. (2019). Overexpression of interleukin-15 exhibits improved glucose tolerance and promotes GLUT4 translocation via AMP-activated protein kinase pathway in skeletal muscle. Biochemical and Biophysical Research Communications, 509, 994-1000. https://doi.org/10.1016/j.bbrc.2019.01.024
Furuichi, Y., Manabe, Y., Takagi, M., Aoki, M., & Fujii, N. L. (2018). Evidence for acute contraction-induced myokine secretion by C2C12 myotubes. PLoS One, 13, e0206146. https://doi.org/10.1371/journal.pone.0206146
Grabstein, K. H., Eisenman, J., Shanebeck, K., Rauch, C., Srinivasan, S., Fung, V., Beers, C., Richardson, J., Schoenborn, M. A., Ahdieh, M., Johnson, L., Alderson, M. R., Watson, J. D., Anderson, D. M., Ahdieh, M., & Giri, J. G. (1994). Cloning of a T cell growth factor that interacts with the β chain of the interleukin-2 receptor. Science, 264, 965-968. https://doi.org/10.1126/science.8178155
Guo, Y., Luan, L., Patil, N. K., & Sherwood, E. R. (2017). Immunobiology of the IL-15/IL-15Rα complex as an antitumor and antiviral agent. Cytokine & Growth Factor Reviews, 38, 10-21.
Huang, P.-L., Hou, M.-S., Wang, S.-W., Chang, C.-L., Liou, Y.-H., & Liao, N.-S. (2015). Skeletal muscle interleukin 15 promotes CD8+ T-cell function and autoimmune myositis. Skeletal Muscle, 5, 33. https://doi.org/10.1186/s13395-015-0058-2
Jakobisiak, M., Golab, J., & Lasek, W. (2011). Interleukin 15 as a promising candidate for tumor immunotherapy. Cytokine & Growth Factor Reviews, 22, 99-108.
Klover, P., Chen, W., Zhu, B. M., & Hennighausen, L. (2009). Skeletal muscle growth and fiber composition in mice are regulated through the transcription factors STAT5a/b: Linking growth hormone to the androgen receptor. FASEB Journal, 23, 3140-3148. https://doi.org/10.1096/fj.08-128215
Liao, W., Lin, J. X., & Leonard, W. J. (2013). Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity, 38, 13-25. https://doi.org/10.1016/j.immuni.2013.01.004
Miyazaki, T., Kawahara, A., Fujii, H., Nakagawa, Y., Minami, Y., Liu, Z.-J., Oishi, I., Silvennoinen, O., Witthuhn, B. A., Ihle, J. N., & Taniguchi, T. (1994). Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits. Science, 266, 1045-1047. https://doi.org/10.1126/science.7973659
Mortier, E., Woo, T., Advincula, R., Gozalo, S., & Ma, A. (2008). IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. Journal of Experimental Medicine, 205, 1213-1225. https://doi.org/10.1084/jem.20071913
Nadeau, L., & Aguer, C. (2019). Interleukin-15 as a myokine: Mechanistic insight into its effect on skeletal muscle metabolism. Applied Physiology, Nutrition and Metabolism, 44, 229-238. https://doi.org/10.1139/apnm-2018-0022
O'Connell, G., Guo, G., Stricker, J., Quinn, L. S., Ma, A., & Pistilli, E. E. (2015). Muscle-specific deletion of exons 2 and 3 of the IL15RA gene in mice: Effects on contractile properties of fast and slow muscles. Journal of Applied Physiology, 118, 437-448. https://doi.org/10.1152/japplphysiol.00704.2014
O'Leary, M. F., Wallace, G. R., Bennett, A. J., Tsintzas, K., & Jones, S. W. (2017). IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development. Scientific Reports, 7, 12997. https://doi.org/10.1038/s41598-017-13479-w
Quinn, L. S., Anderson, B. G., Conner, J. D., Wolden-Hanson, T., & Marcell, T. J. (2014). IL-15 is required for postexercise induction of the pro-oxidative mediators PPARδ and SIRT1 in male mice. Endocrinology, 155, 143-155. https://doi.org/10.1210/en.2013-1645
Quinn, L. S., Anderson, B. G., Strait-Bodey, L., Stroud, A. M., & Argiles, J. M. (2009). Oversecretion of interleukin-15 from skeletal muscle reduces adiposity. American Journal of Physiology. Endocrinology and Metabolism, 296, E191-E202. https://doi.org/10.1152/ajpendo.90506.2008
Quinn, L. S., Haugk, K. L., & Damon, S. E. (1997). Interleukin-15 stimulates C2 skeletal myoblast differentiation. Biochemical and Biophysical Research Communications, 239, 6-10. https://doi.org/10.1006/bbrc.1997.7414
Quinn, L. S., Haugk, K. L., & Grabstein, K. H. (1995). Interleukin-15: A novel anabolic cytokine for skeletal muscle. Endocrinology, 136, 3669-3672. https://doi.org/10.1210/endo.136.8.7628408
Quinn, L. S., Strait-Bodey, L., Anderson, B. G., Argiles, J. M., & Havel, P. J. (2005). Interleukin-15 stimulates adiponectin secretion by 3T3-L1 adipocytes: Evidence for a skeletal muscle-to-fat signaling pathway. Cell Biology International, 29, 449-457. https://doi.org/10.1016/j.cellbi.2005.02.005
Ring, A. M., Lin, J.-X., Feng, D., Mitra, S., Rickert, M., Bowman, G. R., Pande, V. S., Li, P., Moraga, I., Spolski, R., Ozkan, E., Leonard, W. J., & Garcia, K. C. (2012). Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15. Nature Immunology, 13, 1187-1195. https://doi.org/10.1038/ni.2449
Sato, N., Patel, H. J., Waldmann, T. A., & Tagaya, Y. (2007). The IL-15/IL-15Rα on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cells. Proceedings of the National Academy of Sciences of the United States of America, 104, 588-593. https://doi.org/10.1073/pnas.0610115104
Spangenburg, E. E., & Booth, F. W. (2002). Multiple signaling pathways mediate LIF-induced skeletal muscle satellite cell proliferation. American Journal of Physiology. Cell Physiology, 283, C204-C211. https://doi.org/10.1152/ajpcell.00574.2001
Stonier, S. W., & Schluns, K. S. (2010). Trans-presentation: A novel mechanism regulating IL-15 delivery and responses. Immunology Letters, 127, 85-92. https://doi.org/10.1016/j.imlet.2009.09.009
Waldmann, T. A., & Tagaya, Y. (1999). The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens. Annual Review of Immunology, 17, 19-49. https://doi.org/10.1146/annurev.immunol.17.1.19
Wang, X., & Zhao, X. Y. (2021). Transcription factors associated with IL-15 cytokine signaling during NK cell development. Frontiers in Immunology, 12, 610789. https://doi.org/10.3389/fimmu.2021.610789
Woltering, E. A., Barrie, R., O'Dorisio, T. M., Arce, D., Ure, T., Cramer, A., Holmes, D., Robertson, J., & Fassler, J. (1991). Somatostatin analogues inhibit angiogenesis in the chick chorioallantoic membrane. Journal of Surgical Research, 50, 245-251. https://doi.org/10.1016/0022-4804(91)90186-P

Auteurs

Shino Yoshida (S)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Taku Fujimoto (T)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, Institute for Biogenesis Research, University of Hawaii, Honolulu, HI, USA.

Toshimasa Takahashi (T)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Ken Sugimoto (K)

Department of General and Geriatric Medicine, Kawasaki Medical University, Okayama, Japan.

Hiroshi Akasaka (H)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Minoru Tanaka (M)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Kobe, Hyogo, Japan.
Department of Rehabilitation Science, Osaka Health Science University, Osaka, Japan.

Yibin Huang (Y)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Yukiko Yasunobe (Y)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Keyu Xie (K)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Yuri Ohnishi (Y)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Tomohiro Minami (T)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Yoichi Takami (Y)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Koichi Yamamoto (K)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Hiromi Rakugi (H)

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Articles similaires

Arm muscle area is correlated to handgrip strength in postmenopausal women.

Ludwig R Álvarez-Córdova, Reyes Artacho, Peter Chedraui et al.
1.00
Humans Female Hand Strength Postmenopause Cross-Sectional Studies
Humans Transcranial Magnetic Stimulation Male Cerebellum Evoked Potentials, Motor

Classifications MeSH