Endogenous interferon-γ is required for efficient skeletal muscle regeneration
Endogenous interferon-γ is required for efficient skeletal muscle regeneration
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DOI：
10.1152/ajpcell.00568.2007
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发表时间：
2008-05-01
影响因子：
5.5
通讯作者：
Koh, Timothy J.
中科院分区：
文献类型：
--
作者：
Cheng, Ming;Nguyen, Mai-Huong;Koh, Timothy J.
炎症反应被认为在组织愈合中起重要作用。这项研究的假设是，炎症细胞因子干扰素（IFN）-γ在骨骼肌损伤后内源性产生，并促进有效愈合。我们发现，IFN-γ表达在mRNA和蛋白质水平在骨骼肌损伤后，IFN-γ表达的时间过程与巨噬细胞，T细胞，自然杀伤细胞，以及成肌细胞的积累，在受损的肌肉。从损伤的肌肉中分离每种类型的细胞，并在每种细胞类型中检测IFN-γ表达。我们还表明，给野生型小鼠施用IFN-γ受体阻断抗体会损害干扰素应答因子-1的诱导，减少细胞增殖，并减少再生纤维的形成。IFN-γ缺失小鼠表现出与受损的巨噬细胞功能和纤维化发展相关的类似受损的肌肉愈合。体外研究表明，IFN-γ及其受体在C2 C12肌细胞系中表达，并且IFN-γ受体阻断抗体降低了这些肌细胞的增殖和融合。总之，我们的研究结果表明，IFN-γ促进肌肉愈合，部分是通过刺激新的肌肉纤维的形成。
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.