IL-7 is expressed and secreted by human skeletal muscle cells.
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.
Haugen
Fred
F
Department of Nutrition, Institute of Basic Medical Sciences, Medical Faculty, University of Oslo, Blindern, 0317 Oslo, Norway. fred.haugen@medisin.uio.no
Norheim
Frode
F
Lian
Henrik
H
Wensaas
Andreas J
AJ
Dueland
Svein
S
Berg
Ole
O
Funderud
Ane
A
Skålhegg
Bjørn S
BS
Raastad
Truls
T
Drevon
Christian A
CA
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D024510:Muscle Development / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000378:metabolism; D055070:Resistance Training; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism
D015415:Biomarkers; D003470:Culture Media; D015851:Interleukin-7; D012333:RNA, Messenger; D020395:Receptors, Interleukin-7; D018995:Myosin Heavy Chains