Skeletal muscle cell contraction reduces a novel myokine, chemokine (C-X-C motif) ligand 10 (CXCL10): potential roles in exercise-regulated angiogenesis

Abstract

Accumulating evidence indicates that skeletal muscle secrets proteins referred to as myokines and that exercise contributes to their regulation. In this study, we propose that chemokine (C-X-C motif) ligand 10 (CXCL10) functions as a novel myokine. Initially, we stimulated differentiated C2C12 myotubes with or without electrical pulse stimulation (EPS) to identify novel myokines. Cytokine array analysis revealed that CXCL10 secretion was significantly reduced by EPS, which was further confirmed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction analysis. Treadmill experiments in mice identified significant reduction of Cxcl10 gene expression in the soleus muscle. Additionally, contraction-dependent p38 MAPK activation appeared to be involved in this reduction. Furthermore, C2C12 conditioned medium obtained after applying EPS could induce survival of MSS31, a vascular endothelial cell model, which was partially attenuated by the addition of recombinant CXCL10. Overall, our findings suggest CXCL10 as a novel exercise-reducible myokine, to control endothelial cell viability.

CXCL10 as a novel exercise-reducible myokine.

Keywords:

• Exercise
• skeletal muscle
• myokine
• CXCL10

Abbreviations:

• AICAR: 5-aminoimidazole-4-carboxamide-1-β-D- ribofuranoside
• CS: calf serum
• CXCL10: chemokine (C-X-C motif) ligand 10
• EDL: extensor digitorum longus
• ELISA: enzyme-linked immunosorbent assay
• EPS: electrical pulse stimulation
• IP-10: interferon gamma-induced protein 10
• qPCR: quantitative polymerase chain reaction
• quad: quadriceps

Acknowledgements

The authors are grateful to Dr. Anna Oue (Faculty of Food and Nutritional Sciences, Toyo University) for many helpful comments. The authors would like to thank Takuya Shibagaki, Chiho Miyashita and Narumi Komatsu (Faculty of Life Sciences, Toyo University) for technical assistance.