Activation of Platelet NLRP3 Inflammasome in Crohn's Disease.
Activation of Platelet NLRP3 Inflammasome in Crohn's Disease.
复制标题
克罗恩病中血小板 NLRP3 炎性体的激活
DOI：
10.3389/fphar.2021.705325
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发表时间：
2021
影响因子：
5.6
通讯作者：
Xue R
中科院分区：
文献类型：
--
作者：
Zhang G;Chen H;Guo Y;Zhang W;Jiang Q;Zhang S;Han L;Chen S;Xue R
克罗恩病(CD)患者倾向于血小板过度活跃，并增加肠道微血栓形成的风险。然而，CD中血小板过度活跃的机制还不是很清楚。我们研究了活动期CD患者血小板NLRP3炎性小体的组装及其与血小板功能亢进的关系。在这项研究中，实时定量聚合酶链式反应和蛋白质印迹分析发现，与健康受试者相比，活动期CD患者的血小板中ASC、NLRP3和活性caspase-1显著上调。流式细胞仪和酶联免疫吸附试验结果显示，活动期CD患者血清和分离的血小板中IL-1β水平均升高。免疫共沉淀和免疫荧光实验显示，活动期CD患者的血小板中NLRP3炎性小体的组装增加。此外，通过流式细胞仪观察到这些血小板内的ROS水平较高。此外，FCM显示活动期CD患者的血小板P-选择素水平和纤维蛋白原结合率升高。它们与NLRP3炎症体成分的蛋白水平呈正相关。总之，我们的结果表明，ROS-NLRP3炎症体-白介素1β轴可能参与了活动期CD的血小板过度活动。
Patients with Crohn’s disease (CD) are inclined to have platelet hyperactivity and an increased risk of intestinal micro-thrombosis. However, the mechanisms underlying platelet hyperactivity in CD are not well understood. We investigated the assembly of platelet NLRP3 inflammasome in patients with active CD and its correlation with platelet hyperactivity. In this study, Real-time PCR and western blotting analyses uncovered that ASC, NLRP3, and active caspase-1 were significantly upregulated in platelets from patients with active CD compared with healthy subjects. As revealed by flow cytometry (FCM) and ELISA analyses, the levels of interleukin-1β in both serum and isolated platelets were elevated in patients with active CD. Co-immunoprecipitation and immunofluorescence experiments revealed an increased assembly of NLRP3 inflammasome in platelets from patients with active CD. In addition, higher levels of intracellular reactive oxygen species (ROS) were observed in these platelets by FCM. Furthermore, elevated levels of platelet P-selectin exposure and fibrinogen binding were demonstrated in patients with active CD by FCM. They were positively correlated with the protein levels of NLRP3 inflammasome components. Collectively, our results indicate that the ROS-NLRP3 inflammasome-interleukin-1β axis may contribute to platelet hyperactivity in active CD.
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影响因子：
24.5
作者：
Bauer, Christian;Duewell, Peter;Schnurr, Max
通讯作者：
Schnurr, Max
DOI：
10.1084/jem.20100050
发表时间：
2010-05-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allen IC;TeKippe EM;Woodford RM;Uronis JM;Holl EK;Rogers AB;Herfarth HH;Jobin C;Ting JP
通讯作者：
Ting JP
DOI：
10.4291/wjgp.v5.i3.359
发表时间：
2014-08-15
期刊：
World journal of gastrointestinal pathophysiology
影响因子：
--
作者：
Andersen, Nynne Nyboe;Jess, Tine
通讯作者：
Jess, Tine
影响因子：
11.4
作者：
Ratajczak, Mariusz Z.;Adamiak, Mateusz;Lenkiewicz, Anna M.
通讯作者：
Lenkiewicz, Anna M.
DOI：
10.1073/pnas.1620458114
发表时间：
2017-05-02
影响因子：
11.1
作者：
Gupta, Neha;Sahu, Anita;Ashraf, Mohammad Zahid
通讯作者：
Ashraf, Mohammad Zahid