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Synthetic vitamin K analogs inhibit inflammation by targeting the NLRP3 inflammasome.
Cellular & Molecular Immunology ( IF 24.1 ) Pub Date : 2020-09-11 , DOI: 10.1038/s41423-020-00545-z
Xicui Zheng 1, 2 , Yingting Hou 2 , Hongbin He 1, 2 , Yun Chen 2 , Rongbin Zhou 2, 3 , Xiaqiong Wang 1, 2 , Tao Gong 2 , Wei Jiang 2
Affiliation  

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.



中文翻译:

合成维生素 K 类似物通过靶向 NLRP3 炎性体来抑制炎症。

维生素 K 是指一组结构相似的维生素,它们对于正常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仍不清楚。NLRP3炎性体是一种多蛋白复合物,其活化导致IL-1β和IL-18分泌,参与多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 NLRP3 炎性体的选择性强效抑制剂,可特异性阻断 NLRP3 和 ASC 之间的相互作用,从而抑制 NLRP3 炎性体组装。此外,我们表明用维生素 K3 或 K4 治疗可以减轻腹膜炎小鼠模型中炎症的严重程度。

更新日期:2020-09-11
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