Vitamin D stimulates Il-15 synthesis in rodent muscle

Ewendt F, Drewitz F, Althammer M, Eichler C, Brandsch C, Brey S, Winkler T, Wilkens MR, St-Arnaud R, Kreutz M, Stangl GI (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Biochemistry and Biophysics Reports Elsevier

Book Volume: 41

Article Number: 101925

DOI: 10.1016/j.bbrep.2025.101925

Abstract

Besides its classical skeletal function, vitamin D plays a critical role in both skeletal muscle and the immune system. Interleukin-15 (IL-15), which is highly expressed, and secreted complexed with its receptor, IL-15Rα, by skeletal muscle, stimulates the development of immune cells and affects myogenesis and muscle mass. However, little is known about possible regulators of this myokine. To test whether vitamin D could be a regulator of muscle IL-15 and IL-15Rα expression, C2C12 myotubes were treated with vitamin D3 metabolites and analysis were performed in gastrocnemius muscles of rats treated with a single intraperitoneal dose of 1,25(OH)2D3. The role of VDR was investigated by siRNA technique in C2C12 myotubes and in gastrocnemius muscles of vitamin D receptor knockout (Vdr-KO) mice. Treatment of C2C12 myotubes with 1,25(OH)2D3 or 25(OH)D3 increased Il-15 gene expression in a dose-dependent manner and 1,25(OH)2D3 also moderately increased the relative Il-15 protein amount. Rats treated with a single dose of 1,25(OH)2D3 demonstrated a higher mRNA abundance of muscle Il-15 than controls. The 1,25(OH)2D3 effect on Il-15 was considerably weaker in C2C12 myotubes treated with Vdr-specific siRNA. Vdr-KO mice showed significantly lower muscle Il-15 mRNA than WT mice. Il-15Ra mRNA and Il-15/Il-15Rα protein abundance were unaffected by 1,25(OH)2D3-treatment or VDR functionality, and Cyp27b1 activity is not required for 25(OH)D3-mediated Il-15 gene expression. The results provide evidence for a regulatory role of hydroxyvitamin D3 metabolites on the Il-15 synthesis in skeletal muscle cells, which is largely mediated by the VDR.

Authors with CRIS profile

Stefanie Brey Lehrstuhl für Genetik Thomas Winkler Professur für Genetik

Involved external institutions

Universität Regensburg DE Germany (DE) Martin-Luther-Universität Halle-Wittenberg (MLU) DE Germany (DE) Universität Leipzig DE Germany (DE)

How to cite

APA:

Ewendt, F., Drewitz, F., Althammer, M., Eichler, C., Brandsch, C., Brey, S.,... Stangl, G.I. (2025). Vitamin D stimulates Il-15 synthesis in rodent muscle. Biochemistry and Biophysics Reports, 41. https://doi.org/10.1016/j.bbrep.2025.101925

MLA:

Ewendt, Franz, et al. "Vitamin D stimulates Il-15 synthesis in rodent muscle." Biochemistry and Biophysics Reports 41 (2025).

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