IL-7 is expressed and secreted by human skeletal muscle cells

• Published in: American Journal of Physiology: Cell Physiology 2010-04, Vol.298 (4), p.C807-C816
• Main Authors: Haugen, Fred, Norheim, Frode, Lian, Henrik, Wensaas, Andreas J, Dueland, Svein, Berg, Ole, Funderud, Ane, Skålhegg, Bjørn S, Raastad, Truls, Drevon, Christian A
• Format: Article
• Language: English
• Subjects: Adult; Biomarkers - metabolism; Cell Differentiation - physiology; Cell Proliferation; Cells; Cells, Cultured; Culture Media - chemistry; Humans; Interleukin-7 - genetics; Interleukin-7 - metabolism; Male; Middle Aged; Mitochondria; Muscle Development - physiology; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - metabolism; Musculoskeletal system; Myosin Heavy Chains - genetics; Myosin Heavy Chains - metabolism; Proteins; Receptors, Interleukin-7 - genetics; Receptors, Interleukin-7 - metabolism; Resistance Training; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Satellite Cells, Skeletal Muscle - cytology; Satellite Cells, Skeletal Muscle - metabolism
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00094.2009

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.