DHA/AA alleviates LPS-induced Kupffer cells pyroptosis via GPR120 interaction with NLRP3 to inhibit inflammasome complexes assembly.
DHA/AA alleviates LPS-induced Kupffer cells pyroptosis via GPR120 interaction with NLRP3 to inhibit inflammasome complexes assembly.
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DHA/AA 通过 GPR120 与 NLRP3 相互作用抑制炎症小体复合物组装，减轻 LPS 诱导的库普弗细胞焦亡
DOI：
10.1038/s41419-020-03347-3
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发表时间：
2021-01-12
影响因子：
9
通讯作者：
Yang X
中科院分区：
文献类型：
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作者：
Fan G;Li Y;Chen J;Zong Y;Yang X
细胞凋亡是一种新型的细胞程序性死亡，与许多炎症性疾病的发病机制有关。二十二碳六烯酸（DHA）和花生四烯酸（AA）广泛参与炎症病理过程。然而，DHA和AA对枯否细胞焦亡的影响和机制知之甚少。DHA和AA通过逆转NLRP 3炎性复合物、GSDMD、IL-1β、IL-18和PI染色阳性率的表达增加来减轻脂多糖（LPS）诱导的枯否细胞凋亡。接下来，研究表明GPR 120沉默消除了DHA和AA在LPS诱导的库普弗细胞中的抗焦亡作用，表明DHA和AA通过GPR 120信号传导发挥作用。重要的是，GPR 120在LPS刺激下内吞并结合NLRP 3。此外，免疫共沉淀显示DHA和AA促进LPS暴露的Kupffer细胞中GPR 120与NLRP 3之间的相互作用，从而抑制NLRP 3炎性体复合物的自组装。本研究证实DHA和AA通过抑制枯否细胞凋亡减轻肝损伤。提示DHA和AA通过GPR 120与NLRP 3相互作用减轻LPS诱导的枯否细胞焦亡，可能成为一种潜在的治疗肝损伤的方法。
Pyroptosis is a novel type of programmed cell death associated with the pathogenesis of many inflammatory diseases. Docosahexaenoic acid (DHA) and Arachidonic acid (AA) is widely involved in inflammatory pathological processes. However, the effect and mechanism of DHA and AA on pyroptosis in Kupffer cells are poorly understood. The present study demonstrated that DHA and AA ameliorated lipopolysaccharide (LPS)-induced Kupffer cells pyroptosis by reversing the increased expression of NLRP3 inflammasome complex, GSDMD, IL-1β, IL-18, and PI-stained positive rate. Next, the study revealed that GPR120 silencing eliminated the anti-pyroptosis of DHA and AA in LPS-induced Kupffer cells, suggesting that DHA and AA exerted their effect through GPR120 signaling. Importantly, GPR120 endocytose and binds to NLRP3 under LPS stimulation. Furthermore, co-immunoprecipitation showed that DHA and AA promoted the interaction between GPR120 and NLRP3 in LPS-exposed Kupffer cells, thus inhibiting the self-assembly of NLRP3 inflammasome complex. Finally, the study verified that DHA and AA alleviated hepatic injury through inhibiting Kupffer cells pyroptosis in vivo. The findings indicated that DHA and AA alleviated LPS-induced Kupffer cells pyroptosis via GPR120 interaction with NLRP3, it might become a potential therapeutic approach hepatic injury.
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影响因子：
5.8
作者：
Ferrucci, L;Cherubini, A;Guralnik, JM
通讯作者：
Guralnik, JM
影响因子：
4.4
作者：
Li, Pei-zhi;Li, Jin-zheng;He, Kun
通讯作者：
He, Kun
DHA 通过抑制焦亡和激活 PI3K/Akt 通路减轻肝脏缺血再灌注损伤
影响因子：
5
作者：
Li, Ziyi;Zhao, Fazhang;Tong, Liquan
通讯作者：
Tong, Liquan
阻断先天免疫细胞而非肝细胞中的 GSDMD 处理可保护肝脏缺血再灌注损伤
影响因子：
9
作者：
Li, Jichang;Zhao, Jie;Kong, Xiaoni
通讯作者：
Kong, Xiaoni
焦亡是由非选择性gasdermin-D孔驱动的，其形态与MLKL通道介导的坏死性凋亡不同
影响因子：
44.1
作者：
通讯作者：
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