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Publication : Endogenous interferon-gamma is required for efficient skeletal muscle regeneration.

First Author  Cheng M Year  2008
Journal  Am J Physiol Cell Physiol Volume  294
Issue  5 Pages  C1183-91
PubMed ID  18353892 Mgi Jnum  J:136628
Mgi Id  MGI:3796713 Doi  10.1152/ajpcell.00568.2007
Citation  Cheng M, et al. (2008) Endogenous interferon-gamma is required for efficient skeletal muscle regeneration. Am J Physiol Cell Physiol 294(5):C1183-91
abstractText  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.
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