PMID- 38161265 OWN - NLM STAT- Publisher LR - 20240101 IS - 1613-6829 (Electronic) IS - 1613-6810 (Linking) DP - 2023 Dec 31 TI - Monosodium Urate Crystal-Induced Pyroptotic Cell Death in Neutrophil and Macrophage Facilitates the Pathological Progress of Gout. PG - e2308749 LID - 10.1002/smll.202308749 [doi] AB - 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-1beta (IL-1beta). 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. CI - (c) 2023 Wiley-VCH GmbH. FAU - Chen, Chen AU - Chen C AD - State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. AD - School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. FAU - Wang, Jingyun AU - Wang J AD - School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. FAU - Guo, Yiyang AU - Guo Y AD - State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. AD - School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. AD - Frontiers Science Center for Smart Materials Oriented Chemical Engineering, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China. FAU - Li, Min AU - Li M AD - State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. AD - School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. AD - Frontiers Science Center for Smart Materials Oriented Chemical Engineering, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China. FAU - Yang, Kaijun AU - Yang K AD - State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. FAU - Liu, Yang AU - Liu Y AD - State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. AD - School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. AD - Frontiers Science Center for Smart Materials Oriented Chemical Engineering, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China. FAU - Ge, Dan AU - Ge D AD - State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. AD - School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. AD - Frontiers Science Center for Smart Materials Oriented Chemical Engineering, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China. FAU - Liu, Yong AU - Liu Y AD - Department of Hand Surgery, the Fifth Hospital of Harbin, Harbin, 150040, China. FAU - Xue, Changying AU - Xue C AD - School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. FAU - Xia, Tian AU - Xia T AUID- ORCID: 0000-0003-0123-1305 AD - Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095, USA. FAU - Sun, Bingbing AU - Sun B AD - State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. AD - School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China. AD - Frontiers Science Center for Smart Materials Oriented Chemical Engineering, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China. LA - eng GR - DUT21ZD216/Fundamental Research Funds for the Central Universities/ GR - DUT22LAB601/Fundamental Research Funds for the Central Universities/ GR - DUT22YG120/Fundamental Research Funds for the Central Universities/ GR - U22A20455/National Natural Science Foundation of China/ GR - 2022YFC2304305/National Key Research and Development Program of China/ PT - Journal Article DEP - 20231231 PL - Germany TA - Small JT - Small (Weinheim an der Bergstrasse, Germany) JID - 101235338 SB - IM OTO - NOTNLM OT - Dimethyl fumarate OT - Gout OT - Macrophage OT - Monosodium urate crystals OT - Neutrophil, Neutrophil extracellular traps OT - Pyroptosis EDAT- 2024/01/02 11:45 MHDA- 2024/01/02 11:45 CRDT- 2024/01/01 00:02 PHST- 2023/12/09 00:00 [revised] PHST- 2023/09/30 00:00 [received] PHST- 2024/01/02 11:45 [medline] PHST- 2024/01/02 11:45 [pubmed] PHST- 2024/01/01 00:02 [entrez] AID - 10.1002/smll.202308749 [doi] PST - aheadofprint SO - Small. 2023 Dec 31:e2308749. doi: 10.1002/smll.202308749.