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GBP1 exerts inhibitory effects on acute viral myocarditis by inhibiting the inflammatory response of macrophages in mice

机译:GBP1通过抑制小鼠巨噬细胞的炎症反应对急性病毒心肌炎产生抑制作用

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Viral myocarditis (VMC) is a condition that could potentially progress to dilated cardiomyopathy or congestive heart failure, making it the leading cause of the untimely death in young adults. Interferon-induced GBP1 encodes much of the GTPase induced by interferon gamma in many eukaryotic cells. However, little is known regarding the effect of GBP1 on acute VMC (AVMC). Hence, this aim of this study was to assess the effect of GBP1 on AVMC. Once the AVMC mouse models were established, the functional role of GBP1 was determined in AVMC. Serum levels of IL-6, TNF-alpha, and TGF-beta, and expression levels of GBP1, MIF, iNOS, and COX-2 were detected, together with the viability and apoptosis of cardiomyocytes. AVMC mice presented with increased levels of TGF-beta, IL-6, TNF-alpha, MIF, iNOS, and COX-2, as well as cell apoptosis, but lower expression of GBP1 and viability of cardiomyocytes. Restored GBP1 or depleted macrophages resulted in decreased levels of TGF-beta, IL-6, TNF-alpha, MIF, iNOS, and COX-2, as well as cardiomyocyte apoptosis, while increasing cardiomyocyte viability. In conclusion, our results highlight the potential role of GBP1 in inhibiting AVMC development. The experimental results indicate that GBP1 up-regulation and macrophage depletion can alleviate AVMC-related cardial damage by inhibiting inflammatory responses and cardiomyocyte apoptosis while increasing cardiomyocyte viability.
机译:病毒性心肌炎(VMC)是一种可能进展以扩张心肌病或充血性心力衰竭的病症,使其成为年轻成年人不及时死亡的主要原因。干扰素诱导的GBP1编码许多真核细胞中干扰素γ诱导的大部分GTP酶。然而,关于GBP1对急性VMC(AVMC)的影响很少。因此,这项研究的这种目的是评估GBP1对AVMC的影响。一旦建立了AVMC小鼠模型,GBP1的功能作用在AVMC中确定。检测到血清IL-6,TNF-α和TGF-β和表达水平,以及GBP1,MIF,INOS和COX-2的表达水平,以及心肌细胞的活力和凋亡。 AVMC小鼠呈提高TGF-β,IL-6,TNF-α,MIF,INO和COX-2水平,以及细胞凋亡,但细胞凋亡,但是表达GBP1的表达和心肌细胞的可行性。恢复的GBP1或耗尽巨噬细胞导致TGF-β,IL-6,TNF-α,MIF,INO和COX-2水平降低,以及心肌细胞凋亡,同时增加心肌细胞活力。总之,我们的结果突出了GBP1在抑制AVMC发展方面的潜在作用。实验结果表明,GBP1上调和巨噬细胞耗竭可以通过抑制炎症反应和心肌细胞凋亡,同时增加心肌细胞活力来缓解炎症反应和心肌细胞凋亡。

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