NLRP3 deletion protects from hyperoxia-induced acute lung injury
NLRP3 deletion protects from hyperoxia-induced acute lung injury
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DOI：
10.1152/ajpcell.00086.2013
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发表时间：
2013-07-01
影响因子：
5.5
通讯作者：
Kolliputi, Narasaiah
中科院分区：
文献类型：
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作者：
Fukumoto, Jutaro;Fukumoto, Itsuko;Kolliputi, Narasaiah
吸入高浓度氧气是治疗急性肺损伤 (ALI) 的一种方法，可能会意外地导致活性氧 (ROS) 产生和高氧诱导的急性肺损伤 (HALI)。核苷酸结合域和富含亮氨酸重复序列的 PYD 蛋白 3 (NLRP3) 感知 ROS，触发炎症小体激活以及白细胞介素 1 β (IL-1 β) 的产生和分泌。然而，NLRP3 炎症小体在 HALI 中的作用尚不清楚。本研究的主要目的是确定NLRP3基因缺失对炎症反应和肺上皮细胞死亡的影响。野生型 (WT) 和 NLRP3(-/-) 小鼠暴露于 100% O-2 48-72 小时。检查支气管肺泡灌洗液和肺组织的促炎细胞因子产生和肺部炎症。与 WT 小鼠相比，NLRP3(-/-) 小鼠高氧诱导的肺病理评分受到抑制。在NLRP3(-/-)小鼠中，高氧诱导的炎症细胞募集以及IL-1β、TNFα、巨噬细胞炎症蛋白2和单核细胞趋化蛋白1的升高均减弱。与 WT 对照相比，NLRP3 缺失降低了肺上皮细胞死亡和 caspase-3 水平，并抑制了 NF-κ B 水平。总而言之，这项研究首次证明 NLRP3 缺陷小鼠能够抑制炎症反应并减弱肺上皮细胞对 HALI 的凋亡。
Inspiration of a high concentration of oxygen, a therapy for acute lung injury (ALI), could unexpectedly lead to reactive oxygen species (ROS) production and hyperoxia-induced acute lung injury (HALI). Nucleotide-binding domain and leucine-rich repeat PYD-containing protein 3 (NLRP3) senses the ROS, triggering inflammasome activation and interleukin-1 beta (IL-1 beta) production and secretion. However, the role of NLRP3 inflammasome in HALI is unclear. The main aim of this study is to determine the effect of NLRP3 gene deletion on inflammatory response and lung epithelial cell death. Wild-type (WT) and NLRP3(-/-) mice were exposed to 100% O-2 for 48-72 h. Bronchoalveolar lavage fluid and lung tissues were examined for proinflammatory cytokine production and lung inflammation. Hyperoxia-induced lung pathological score was suppressed in NLRP3(-/-) mice compared with WT mice. Hyperoxia-induced recruitment of inflammatory cells and elevation of IL-1 beta, TNF alpha, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 were attenuated in NLRP3(-/-) mice. NLRP3 deletion decreased lung epithelial cell death and caspase-3 levels and a suppressed NF-kappa B levels compared with WT controls. Taken together, this research demonstrates for the first time that NLRP3-deficient mice have suppressed inflammatory response and blunted lung epithelial cell apoptosis to HALI.