RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice.
RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice.
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RIP3 依赖性 NLRP3 炎性体激活与小鼠急性肺损伤有关
DOI：
10.1186/s12967-018-1606-4
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发表时间：
2018-08-20
影响因子：
7.4
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Chen J;Wang S;Fu R;Zhou M;Zhang T;Pan W;Yang N;Huang Y
NLRP 3炎性体参与了急性肺损伤（ALI）的炎症反应。RIP 3触发的NLRP 3炎性小体激活独立于坏死性凋亡诱导最近已被记录。本研究旨在探讨RIP 3在ALI发生发展过程中NLRP 3炎性体活化中的作用。用选择性RIP 3抑制剂GSK 872研究了RIP 3在脂多糖（LPS）诱导的ALI小鼠模型中NLRP 3炎性小体激活中的作用。在人单核细胞系THP-1中研究了NLRP 3炎性小体活化的机制。通过流式细胞术或蛋白质印迹法测量NLRP 3炎性小体和坏死性凋亡。使用免疫沉淀和Duolink®原位检测来询问RIP 3-NLRP 3相互作用。在LPS诱导的ALI小鼠的肺中观察到坏死性凋亡和NLRP 3炎性体途径的显著上调。GSK 872显著抑制坏死性凋亡和NLRP 3的激活，减少IL-1β和IL-18的产生和炎性细胞浸润，从而显著改善肺损伤。这两个过程在间质巨噬细胞和CD 11b+单核-巨噬细胞/树突状细胞中显示出活性。在THP-1细胞中，LPS/ATP刺激增强了RIP 3和NLRP 3的相互作用，导致IL-1β和IL-18的产生。这种RIP 3-NLRP 3相互作用被GSK 872显著抑制。综上所述，这些结果表明RIP 3参与LPS诱导的ALI中浸润巨噬细胞中的NLRP 3炎性体活化。该过程在LPS诱导的肺损伤中起重要的致病作用。本文的在线版本（10.1186/s12967-018-1606-4）包含补充材料，可供授权用户使用。
NLRP3 inflammasome is involved in the inflammatory responses during acute lung injury (ALI). RIP3 triggered NLRP3 inflammasome activation independent of necroptosis induction has recently been documented. In this study, the role of RIP3 in the activation of NLRP3 inflammasome in the development of ALI was investigated. A selective RIP3 inhibitor GSK872 was used to investigate the roles of RIP3 in NLRP3 inflammasome activation in the lipopolysaccharide (LPS) induced ALI mouse model. The mechanism of NLRP3 inflammasome activation was investigated in the human monocytic cell line THP-1. NLRP3 inflammasome and necroptosis were measured by flow cytometry or western blot. RIP3–NLRP3 interaction was interrogated using immunoprecipitation and the Duolink® In situ detection. Significant upregulation of both necroptosis and NLRP3 inflammasome pathways were observed in the lungs of mice with LPS induced ALI. GSK872 significantly suppressed the activation of necroptosis and NLRP3 activation with reduction of IL-1β and IL-18 production and inflammatory cells infiltration, resulting in a significant amelioration of lung injury. These two processes were shown to be active in interstitial macrophages and CD11b+ monocyte–macrophages/dendritic cells. In THP-1 cells, RIP3 and NLRP3 interaction was enhanced by LPS/ATP stimulation resulting in IL-1β and IL-18 production. This RIP3–NLRP3 interaction was significantly inhibited by GSK872. Taking together, these results show that RIP3 participates in the NLRP3 inflammasome activation in infiltrating macrophages in ALI induced by LPS. This process plays a significant pathogenic role in LPS-induced lung injury. The online version of this article (10.1186/s12967-018-1606-4) contains supplementary material, which is available to authorized users.
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受体相互作用蛋白 3 介导的坏死性凋亡促进脂多糖诱导的小鼠炎症和急性呼吸窘迫综合征
影响因子：
3.7
作者：
Wang L;Wang T;Li H;Liu Q;Zhang Z;Xie W;Feng Y;Socorburam T;Wu G;Xia Z;Wu Q
通讯作者：
Wu Q
影响因子：
5.1
作者：
Liu Z;Zhao H;Liu W;Li T;Wang Y;Zhao M
通讯作者：
Zhao M
影响因子：
5.6
作者：
Wang S;Zhao J;Wang H;Liang Y;Yang N;Huang Y
通讯作者：
Huang Y
影响因子：
32.4
作者：
Moriwaki, Kenta;Balaji, Sakthi;McQuade, Thomas;Malhotra, Nidhi;Kang, Joonsoo;Chan, Francis Ka-Ming
通讯作者：
Chan, Francis Ka-Ming
影响因子：
16.6
作者：
Lawlor, Kate E.;Khan, Nufail;Mildenhall, Alison;Gerlic, Motti;Croker, Ben A.;D'Cruz, Akshay A.;Hall, Cathrine;Spall, Sukhdeep Kaur;Anderton, Holly;Masters, Seth L.;Rashidi, Maryam;Wicks, Ian P.;Alexander, Warren S.;Mitsuuchi, Yasuhiro;Benetatos, Christopher A.;Condon, Stephen M.;Wong, W. Wei-Lynn;Silke, John;Vaux, David L.;Vince, James E.
通讯作者：
Vince, James E.