NLRP3 inflammasome activation in cigarette smoke priming for Pseudomonas aeruginosa-induced acute lung injury.
NLRP3 inflammasome activation in cigarette smoke priming for Pseudomonas aeruginosa-induced acute lung injury.
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NLRP3炎性小体在香烟烟雾致敏铜绿假单胞菌诱导的急性肺损伤中的激活作用
DOI：
10.1016/j.redox.2022.102467
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发表时间：
2022-11
期刊：
影响因子：
11.4
通讯作者：
Lu, Qing
中科院分区：
文献类型：
--
作者：
White, Alexis;Wang, Zhengke;Wang, Xing;King, Michelle;Guo, Cynthia;Mantsounga, Chris;Ayala, Alfred;Morrison, Alan R.;Choudhary, Gaurav;Sellke, Frank;Chambers, Eboni;Ware, Lorraine B.;Rounds, Sharon;Lu, Qing
关键词：
越来越多的人认识到，接触香烟烟雾会增加危重病人和动物急性呼吸窘迫综合征（ARDS）的发病率和严重程度。然而，其机制尚不清楚。本研究旨在通过临床前动物模型和转基因小鼠，探讨CS对铜绿假单胞菌引发的急性肺损伤的启动作用机制。我们证明，CS损害了铜绿假单胞菌诱导的线粒体自噬通量，促进了p62的积累，并加剧了铜绿假单胞菌引发的肺泡巨噬细胞线粒体损伤和NLRP3炎性体的激活；这种效应与急性肺损伤和死亡率增加有关。药物抑制caspase-1（炎性体的一种成分），减轻CS引发的铜绿假单胞菌引发的急性肺损伤，提高动物存活率。IL-1β是炎性小体激活的下游成分，IL-1β的整体或骨髓特异性敲除也可以减轻CS引发的铜绿假单胞菌引发的急性肺损伤。我们的研究结果表明NLRP3炎性小体激活是CS引发铜绿假单胞菌引发急性肺损伤的重要机制。（总字数155）。香烟烟雾暴露可促进铜绿假单胞菌感染小鼠的急性肺损伤/急性呼吸窘迫综合征（ARDS）香烟烟雾暴露加剧了铜绿假单胞菌引发的线粒体损伤和肺泡巨噬细胞NLRP3炎性体的激活；炎性小体阻断可减轻香烟烟雾引发的铜绿假单胞菌引发的急性肺损伤，提示NLRP3炎性小体激活在这一过程中发挥关键作用。本研究的主要亮点：
It is increasingly recognized that cigarette smoke (CS) exposure increases the incidence and severity of acute respiratory distress syndrome (ARDS) in critical ill humans and animals. However, the mechanism(s) is not well understood. This study aims to investigate mechanism underlying the priming effect of CS on Pseudomonas aeruginosa-triggered acute lung injury, by using pre-clinic animal models and genetically modified mice. We demonstrated that CS impaired P. aeruginosa-induced mitophagy flux, promoted p62 accumulation, and exacerbated P. aeruginosa-triggered mitochondrial damage and NLRP3 inflammasome activation in alveolar macrophages; an effect associated with increased acute lung injury and mortality. Pharmacological inhibition of caspase-1, a component of inflammasome, attenuated CS primed P. aeruginosa-triggered acute lung injury and improved animal survival. Global or myeloid-specific knockout of IL-1β, a downstream component of inflammasome activation, also attenuated CS primed P. aeruginosa-triggered acute lung injury. Our results suggest that NLRP3 inflammasome activation is an important mechanism for CS primed P. aeruginosa-triggered acute lung injury. (total words: 155). Cigarette smoke exposure promotes acute lung injury/acute respiratory distress syndrome (ARDS) in mice infected with P. aeruginosa; Cigarette smoke exposure exacerbates P. aeruginosa-triggered mitochondrial damage and NLRP3 inflammasome activation in alveolar macrophages; Blockage of inflammasome attenuates cigarette smoke primed P. aeruginosa-triggered acute lung injury, suggesting a key role of NLRP3 inflammasome activation in this process. Major highlights of this study:
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DOI：
10.1165/rcmb.2015-0017oc
发表时间：
2016-03-01
影响因子：
6.4
作者：
Basilico, Paola;Cremona, Tiziana P.;Benarafa, Charaf
通讯作者：
Benarafa, Charaf
FIP200通过调节HMGB1细胞内易位参与鼠假单胞菌感染。
DOI：
10.1159/000362954
发表时间：
2014
期刊：
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
影响因子：
--
作者：
Li Y;Gan CP;Zhang S;Zhou XK;Li XF;Wei YQ;Yang JL;Wu M
通讯作者：
Wu M
DOI：
10.1165/rcmb.2015-0149oc
发表时间：
2016-05-01
影响因子：
6.4
作者：
Borgas, Diana;Chambers, Eboni;Lu, Qing
通讯作者：
Lu, Qing
影响因子：
9.6
作者：
Alexander, Laura E. Crotty;Shin, Stephanie;Hwang, John H.
通讯作者：
Hwang, John H.
DOI：
10.1164/rccm.200311-1521oc
发表时间：
2004-12-01
影响因子：
24.7
作者：
Drannik, AG;Pouladi, MA;Stämpfli, MR
通讯作者：
Stämpfli, MR