Endogenous interferon-gamma is required for efficient skeletal muscle regeneration.
The inflammatory response is thought to play important roles in tissue healing. The hypothesis of this study was that the inflammatory cytokine interferon (IFN)-gamma is produced endogenously following skeletal muscle injury and promotes efficient healing. We show that IFN-gamma is expressed at both mRNA and protein levels in skeletal muscle following injury, and that the time course of IFN-gamma expression correlated with the accumulation of macrophages, T-cells, and natural killer cells, as well as myoblasts, in damaged muscle. Cells of each type were isolated from injured muscle, and IFN-gamma expression was detected in each cell type. We also demonstrate that administration of an IFN-gamma receptor blocking antibody to wild-type mice impaired induction of interferon response factor-1, reduced cell proliferation, and decreased formation of regenerating fibers. IFN-gamma null mice showed similarly impaired muscle healing associated with impaired macrophage function and development of fibrosis. In vitro studies demonstrated that IFN-gamma and its receptor are expressed in the C2C12 muscle cell line, and that the IFN-gamma receptor blocking antibody reduced proliferation and fusion of these muscle cells. In summary, our results indicate that IFN-gamma promotes muscle healing, in part, by stimulating formation of new muscle fibers.
Cheng
Ming
M
Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, USA.
Nguyen
Mai-Huong
MH
Fantuzzi
Giamila
G
Koh
Timothy J
TJ
D000818:Animals; D018929:Cell Culture Techniques; D002455:Cell Division; D004179:Cobra Cardiotoxin Proteins / Q000633:toxicity; D017931:DNA Primers; D005552:Forelimb; D007249:Inflammation; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007381:Intermediate Filament Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017471:Receptors, Interferon / Q000037:antagonists & inhibitors; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000096743:Interferon gamma Receptor
D004179:Cobra Cardiotoxin Proteins; D017931:DNA Primers; D007371:Interferon-gamma; D007381:Intermediate Filament Proteins; D009124:Muscle Proteins; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C503782:Sync protein, mouse