Monosodium Urate Crystal‐Induced Pyroptotic Cell Death in Neutrophil and Macrophage Facilitates the Pathological Progress of Gout

上睑下垂 炎症体 痛风 中性粒细胞胞外陷阱 程序性细胞死亡 细胞外 坏死性下垂 巨噬细胞 炎症 细胞生物学 化学 细胞凋亡 材料科学 免疫学 医学 生物 生物化学 体外
作者
Chen Chen,Jingyun Wang,Yiyang Guo,Min Li,Kaijun Yang,Yang Liu,Di Ge,Yong Liu,Changying Xue,Tian Xia,Bingbing Sun
出处
期刊:Small [Wiley]
卷期号:20 (23) 被引量:6
标识
DOI:10.1002/smll.202308749
摘要

Abstract Monosodium urate (MSU) crystal deposition in joints can lead to the infiltration of neutrophils and macrophages, and their activation plays a critical role in the pathological progress of gout. However, the role of MSU crystal physicochemical properties in inducing cell death in neutrophil and macrophage is still unclear. In this study, MSU crystals of different sizes are synthesized to explore the role of pyroptosis in gout. It is demonstrated that MSU crystals induce size‐dependent pyroptotic cell death in bone marrow‐derived neutrophils (BMNs) and bone marrow‐derived macrophages (BMDMs) by triggering NLRP3 inflammasome‐dependent caspase‐1 activation and subsequent formation of N‐GSDMD. Furthermore, it is demonstrated that the size of MSU crystal also determines the formation of neutrophil extracellular traps (NETs) and aggregated neutrophil extracellular traps (aggNETs), which are promoted by the addition of interleukin‐1β (IL‐1β). Based on these mechanistic understandings, it is shown that N‐GSDMD oligomerization inhibitor, dimethyl fumarate (DMF), inhibits MSU crystal‐induced pyroptosis in BMNs and J774A.1 cells, and it further alleviates the acute inflammatory response in MSU crystals‐induced gout mice model. This study elucidates that MSU crystal‐induced pyroptosis in neutrophil and macrophage is critical for the pathological progress of gout, and provides a new therapeutic approach for the treatment of gout.
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