Deletion of Nlrp3 protects from inflammation-induced skeletal muscle atrophy.
Deletion of Nlrp3 protects from inflammation-induced skeletal muscle atrophy.
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DOI：
10.1186/s40635-016-0115-0
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发表时间：
2017-12
影响因子：
3.5
通讯作者：
Fielitz J
中科院分区：
文献类型：
--
作者：
Huang N;Kny M;Riediger F;Busch K;Schmidt S;Luft FC;Slevogt H;Fielitz J
危重病人出现萎缩性肌肉衰竭，增加发病率和死亡率。白介素-1β (IL-1β)在败血症早期被激活。IL-1β是否直接作用于肌肉细胞以及其抑制作用是否能防止肌肉萎缩尚不清楚。我们的目的是研究IL-1β通过Nlrp3炎症小体激活是否参与炎症诱导的萎缩。我们进行了实验研究和前瞻性动物试验。通过分析IL-1β对分化的C2C12肌细胞的基因和蛋白表达及萎缩反应，探讨IL-1β对C2C12肌细胞的影响。在Nlrp3基因敲除小鼠和野生型小鼠中，采用盲肠结扎和穿刺手术诱导多微生物脓毒症。采用骨骼肌形态学、基因和蛋白表达及萎缩标志物分析萎缩反应。免疫染色和报告基因分析表明，IL-1β信号在肌细胞中含有并活跃。免疫染色和报告基因检测显示，IL-1β信号在肌细胞中含有并活跃。IL-1β增加il - 6和atrogene基因表达，导致肌细胞萎缩。Nlrp3基因敲除小鼠脓毒症时血清IL-1β水平降低。通过肌肉形态、器官重量、基因表达和蛋白质含量的测定，与脓毒症野生型小鼠相比，脓毒症Nlrp3基因敲除小鼠术后96小时的肌肉萎缩有所减轻。IL-1β在脓毒症中直接作用于肌细胞导致萎缩。通过靶向Nlrp3抑制IL-1β激活可能有助于预防危重患者炎症性肌肉衰竭。本文的在线版本（doi:10.1186/s40635-016- 015 -0）包含补充材料，授权用户可以使用。
Critically ill patients develop atrophic muscle failure, which increases morbidity and mortality. Interleukin-1β (IL-1β) is activated early in sepsis. Whether IL-1β acts directly on muscle cells and whether its inhibition prevents atrophy is unknown. We aimed to investigate if IL-1β activation via the Nlrp3 inflammasome is involved in inflammation-induced atrophy. We performed an experimental study and prospective animal trial. The effect of IL-1β on differentiated C2C12 muscle cells was investigated by analyzing gene-and-protein expression, and atrophy response. Polymicrobial sepsis was induced by cecum ligation and puncture surgery in Nlrp3 knockout and wild type mice. Skeletal muscle morphology, gene and protein expression, and atrophy markers were used to analyze the atrophy response. Immunostaining and reporter-gene assays showed that IL-1β signaling is contained and active in myocytes. Immunostaining and reporter gene assays showed that IL-1β signaling is contained and active in myocytes. IL-1β increased Il6 and atrogene gene expression resulting in myocyte atrophy. Nlrp3 knockout mice showed reduced IL-1β serum levels in sepsis. As determined by muscle morphology, organ weights, gene expression, and protein content, muscle atrophy was attenuated in septic Nlrp3 knockout mice, compared to septic wild-type mice 96 h after surgery. IL-1β directly acts on myocytes to cause atrophy in sepsis. Inhibition of IL-1β activation by targeting Nlrp3 could be useful to prevent inflammation-induced muscle failure in critically ill patients. The online version of this article (doi:10.1186/s40635-016-0115-0) contains supplementary material, which is available to authorized users.