title: Endogenous interferon-gamma is required for efficient skeletal muscle regeneration.
abstract: 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.
authors: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors: Ming
authors: M
authors: Cheng
authors: Mai-Huong
authors: MH
authors: Nguyen
authors: Giamila
authors: G
authors: Fantuzzi
authors: Timothy J
authors: TJ
authors: Koh
mesh_terms: 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
chemical_list: 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