ROS-Mediated NLRP3 Inflammasome Activity Is Essential for Burn-Induced Acute Lung Injury.
ROS-Mediated NLRP3 Inflammasome Activity Is Essential for Burn-Induced Acute Lung Injury.
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ROS 介导的 NLRP3 炎症小体活性对于烧伤引起的急性肺损伤至关重要。
DOI：
10.1155/2015/720457
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发表时间：
2015
影响因子：
4.6
通讯作者：
Hu D
中科院分区：
文献类型：
--
作者：
Han S;Cai W;Yang X;Jia Y;Zheng Z;Wang H;Li J;Li Y;Gao J;Fan L;Hu D
NLRP 3炎性体是引发急性无菌性炎症所必需的。然而，其在烧伤引起的急性肺损伤（ALI）发病机制中的作用尚不清楚。本研究旨在确定NLRP 3炎性体的作用和参与烧伤诱导的ALI的信号通路。我们观察到大鼠烧伤后肺表现出增强的炎性小体活性，这可以通过NLRP 3表达水平和Caspase-1活性的增加以及炎性细胞因子的增加来证明。BAY 11 -7082对NLRP 3炎性体的抑制减弱了烧伤诱导的ALI，如通过伴随的组织病理学变化的缓解和髓过氧化物酶（MPO）活性、大鼠肺组织中的炎性细胞因子和支气管肺泡灌洗液（BALF）中的蛋白质浓度的降低所证明的。在体外实验中，我们使用烧伤血清激发的AM（肺泡巨噬细胞）来模拟烧伤后的微环境，并注意到血清显著上调NLRP 3炎性体信号传导和活性氧（ROS）产生。使用ROS清除剂N-乙酰半胱氨酸（NAC）部分逆转了暴露于烧伤血清的细胞中的NLRP 3炎性小体活性。这些结果表明，NLRP 3炎性小体在烧伤诱导的ALI中起着重要作用，并且烧伤诱导的NLRP 3炎性小体活性是部分ROS依赖性过程。靶向该轴可能代表治疗烧伤诱导的ALI的有前景的治疗策略。
The NLRP3 inflammasome is necessary for initiating acute sterile inflammation. However, its role in the pathogenesis of burn-induced acute lung injury (ALI) is unknown. This study aimed to determine the role of the NLRP3 inflammasome and the signaling pathways involved in burn-induced ALI. We observed that the rat lungs exhibited enhanced inflammasome activity after burn, as evidenced by increased levels of NLRP3 expression and Caspase-1 activity and augmented inflammatory cytokines. Inhibition of NLRP3 inflammasome by BAY11-7082 attenuated burn-induced ALI, as demonstrated by the concomitant remission of histopathologic changes and the reduction of myeloperoxidase (MPO) activity, inflammatory cytokines in rat lung tissue, and protein concentrations in the bronchoalveolar lavage fluid (BALF). In the in vitro experiments, we used AMs (alveolar macrophages) challenged with burn serum to mimic the postburn microenvironment and noted that the serum significantly upregulated NLRP3 inflammasome signaling and reactive oxygen species (ROS) production. The use of ROS scavenger N-acetylcysteine (NAC) partially reversed NLRP3 inflammasome activity in cells exposed to burn serum. These results indicate that the NLRP3 inflammasome plays an essential role in burn-induced ALI and that burn-induced NLRP3 inflammasome activity is a partly ROS-dependent process. Targeting this axis may represent a promising therapeutic strategy for the treatment of burn-induced ALI.