Epigenetic coordination of acute systemic inflammation: potential therapeutic targets.
Epigenetic coordination of acute systemic inflammation: potential therapeutic targets.
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DOI：
10.1586/1744666x.2014.943192
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发表时间：
2014-09
影响因子：
4.4
通讯作者：
McCall CE
中科院分区：
文献类型：
--
作者：
Vachharajani V;Liu T;McCall CE
数千个基因的表观遗传重编程指导急性全身性炎症的过程，这在脓毒症期间失调时是高度致命的。目前尚无针对脓毒症的分子治疗方法。一个新的概念支持脓毒症是一种免疫代谢疾病，并且核表观遗传调节因子Sirtuin 1（SIRT-1）的失控，NAD+传感器在脓毒症期间指导免疫和代谢途径。SIRT-1作为体内平衡检查点，控制微血管界面处脓毒症的高炎症和低炎症反应，其传播炎症损伤以引起多器官衰竭。修饰SIRT-1活性，可以预防或治疗小鼠中已建立的脓毒症，可能提供通过表观遗传学恢复免疫代谢稳态来治疗脓毒症的新途径。
Epigenetic reprogramming of thousands of genes directs the course of acute systemic inflammation, which is highly lethal when dysregulated during sepsis. No molecular-based treatments for sepsis are available. A new concept supports that sepsis is an immunometabolic disease and that loss of control of nuclear epigenetic regulator Sirtuin 1 (SIRT-1), a NAD+ sensor directs immune and metabolic pathways during sepsis. SIRT-1, acting as homeostasis checkpoint, controls hyper and hypo inflammatory responses of sepsis at the microvascular interface, which disseminates inflammatory injury to cause multiple organ failure. Modifying SIRT-1 activity, which can prevent or treat established sepsis in mice, may provide a new way treat sepsis by epigenetically restoring immunometabolic homeostasis.