The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Cell Mol Immunol. 2021 Oct;18(10):2422-2430. doi: 10.1038/s41423-020-00545-z. Epub 2020 Sep 11.
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.
维生素 K 是一组结构相似的维生素，对正常凝血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 可能具有抗炎特性，但其抗炎作用的潜在机制尚不清楚。NLRP3 炎性体是一种多蛋白复合物，其激活导致 IL-1β 和 IL-18 的分泌，并有助于各种人类炎症性疾病的发病机制。在这里，我们表明合成维生素 K3 和 K4 是 NLRP3 炎性体的选择性、有效抑制剂，并且特异性阻断 NLRP3 和 ASC 之间的相互作用，从而抑制 NLRP3 炎性体的组装。此外，我们表明，用维生素 K3 或 K4 治疗可减轻腹膜炎小鼠模型中炎症的严重程度。我们的结果表明，维生素 K3 和 K4 通过抑制 NLRP3 炎性体的激活发挥抗炎作用，并表明维生素 K 补充可能是 NLRP3 相关炎症性疾病的一种治疗选择。
