NLRP3 inflammasome activation is essential for paraquat-induced acute lung injury.
NLRP3 inflammasome activation is essential for paraquat-induced acute lung injury.
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DOI：
10.1007/s10753-014-0048-2
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发表时间：
2015-03
期刊：
影响因子：
5.1
通讯作者：
Zhao M
中科院分区：
文献类型：
--
作者：
Liu Z;Zhao H;Liu W;Li T;Wang Y;Zhao M
天然免疫反应在百草枯诱导的急性肺损伤中很重要，但涉及的确切途径尚未阐明。本研究的目的是确定NLRP 3炎性体在该过程中的具体作用。百草枯（PQ）腹腔注射诱导急性肺损伤。检测PQ给药后4、8、24、72 h大鼠肺组织NLRP 3炎性小体（包括NLRP 3、ASC和caspase-1）mRNA和蛋白表达以及BALF中IL-1β和IL-18水平。此外，在PQ暴露前1 h，分别用10、30和50 mg/kg NLRP 3炎性体阻断剂格列本脲预处理大鼠。PQ给药后72 h，观察肺组织病理学变化，BALF中NLRP 3、ASC和caspase-1蛋白表达，以及IL-1β和IL-18等细胞因子的分泌。PQ中毒组大鼠NLRP 3炎性小体（包括NLRP 3、ASC、caspase-1）表达及细胞因子IL-1β、IL-18水平均显著高于对照组。NLRP 3炎性体阻断剂格列本脲预处理减轻肺水肿，抑制BALF中NLRP 3、ASC和caspase-1的活化，并降低IL-1β和IL-18水平。在体外实验中，格列本脲可减弱百草枯处理的RAW 264. 7小鼠巨噬细胞分泌的IL-1β和IL-18。综上所述，百草枯可通过NLRP 3-ASC-caspase-1途径诱导IL-1β/IL-18分泌，NLRP 3炎性小体在百草枯诱导的急性肺损伤中起重要作用。
The innate immune response is important in paraquat-induced acute lung injury, but the exact pathways involved are not elucidated. The objectives of this study were to determine the specific role of the NLRP3 inflammasome in the process. Acute lung injury was induced by administering paraquat (PQ) intraperitoneally. NLRP3 inflammasome including NLRP3, ASC, and caspase-1 mRNA and protein expression in lung tissue and IL-1β and IL-18 levels in BALF were detected at 4, 8, 24, and 72 h after PQ administration in rats. Moreover, rats were pretreated with 10, 30, and 50 mg/kg NLRP3 inflammasome blocker glybenclamide, respectively, 1 h before PQ exposure. At 72 h after PQ administration, lung histopathology changes, NLRP3, ASC, and caspase-1 protein expression, as well as secretion of cytokines including IL-1β and IL-18 in BALF were investigated. The NLRP3 inflammasome including NLRP3, ASC, caspase-1 expression, and cytokines IL-1β and IL-18 levels in PQ poisoning rats were significantly higher than that in the control group. NLRP3 inflammasome blocker glybenclamide pretreatment attenuated lung edema, inhibited the NLRP3, ASC, and caspase-1 activation, and reduced IL-1β and IL-18 levels in BALF. In the in vitro experiments, IL-1β and IL-18 secreted from RAW264.7 mouse macrophages treated with paraquat were attenuated by glybenclamide. In conclusion, paraquat can induce IL-1β/IL-18 secretion via NLRP3-ASC-caspase-1 pathway, and the NLRP3 inflammasome is essential for paraquat-induced acute lung injury.
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影响因子：
29.7
作者：
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通讯作者：
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