Synthetic vitamin K analogs inhibit inflammation by targeting the NLRP3 inflammasome
Synthetic vitamin K analogs inhibit inflammation by targeting the NLRP3 inflammasome
复制标题
合成维生素 K 类似物通过靶向 NLRP3 炎症小体抑制炎症
DOI：
10.1038/s41423-020-00545-z
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发表时间：
2020-09-11
影响因子：
24.1
通讯作者：
Jiang, Wei
中科院分区：
文献类型：
--
作者：
Zheng, Xicui;Hou, Yingting;Jiang, Wei
维生素K是指一组结构相似的维生素，它们对适当的血液凝固以及骨骼和心血管健康至关重要。先前的研究表明，维生素K也可能具有抗炎特性，尽管其抗炎作用的潜在机制尚不清楚。NLRP 3炎性体是一种多蛋白复合物，其活化导致IL-1β和IL-18分泌，并有助于各种人类炎性疾病的发病机制。在这里，我们表明合成维生素K3和K4是NLRP 3炎性体的选择性、有效的抑制剂，并且特异性地阻断NLRP 3和ASC之间的相互作用，从而抑制NLRP 3炎性体组装。此外，我们表明，维生素K3或K4治疗减轻腹膜炎小鼠模型中炎症的严重程度。我们的研究结果表明，维生素K3和K4通过抑制NLRP 3炎性小体激活发挥其抗炎作用，并表明维生素K补充剂可能是NLRP 3相关炎性疾病的治疗选择。
Vitamin K refers to a group of structurally similar vitamins that are essential for proper blood coagulation, as well as bone and cardiovascular health. Previous studies have indicated that vitamin K may also have anti-inflammatory properties, although the underlying mechanisms of its anti-inflammatory effects remain unclear. The NLRP3 inflammasome is a multiprotein complex, and its activation leads to IL-1β and IL-18 secretion and contributes to the pathogenesis of various human inflammatory diseases. Here, we show that synthetic vitamins K3 and K4 are selective, potent inhibitors of the NLRP3 inflammasome and specifically block the interaction between NLRP3 and ASC, thereby inhibiting NLRP3 inflammasome assembly. Moreover, we show that treatment with vitamin K3 or K4 attenuates the severity of inflammation in a mouse model of peritonitis. Our results demonstrate that vitamins K3 and K4 exert their anti-inflammatory effects by inhibiting NLRP3 inflammasome activation and indicate that vitamin K supplementation may be a treatment option for NLRP3-associated inflammatory diseases.