The airway epithelium nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome is activated by urban particulate matter
The airway epithelium nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome is activated by urban particulate matter
复制标题
DOI：
10.1016/j.jaci.2011.11.033
复制
发表时间：
2012-04-01
影响因子：
14.2
通讯作者：
Knight, Darryl A.
中科院分区：
文献类型：
--
作者：
Hirota, Jeremy A.;Hirota, Simon A.;Knight, Darryl A.
背景：气道上皮是抵御吸入性损伤的第一道防线，因此必须能够协调适当的炎症和免疫反应。目的：我们试图验证这样的假设：核苷酸结合域和富含亮氨酸重复蛋白 3 (NLRP3) 炎症小体（一种细胞内危险感知复合物）在气道上皮介导的城市颗粒物 (PM) 暴露免疫反应中发挥关键作用。方法：在本研究中，我们 (1) 鉴定了 NLRP3 和 caspase-1 在人气道上皮支气管和原代细胞中的表达，(2) 表征了 NLRP3人气道上皮炎症小体介导的 IL-1 β 生成响应 PM，以及 (3) 使用野生型和 Nlrp3(-/-) 小鼠进行体内 PM 暴露实验。结果：我们的结果表明，人气道上皮含有功能性 NLRP3 炎症小体，该炎症小体通过 caspase-1 裂解和产生 IL-1 β 来响应 PM 暴露。 Nlrp3(-/-) 和野生型小鼠体内暴露于 PM 表明肺中 NLRP3 依赖性 IL-1 β 产生、气道中性粒细胞增多以及胸内淋巴结中 CD11c(+hi)/MHC II+hi 细胞数量增加。结论：我们的研究首次描述了气道上皮 NLRP3 炎性体介导的对 PM 暴露的免疫反应，这可能对哮喘和其他肺部疾病患者产生影响疾病。 （《过敏临床免疫杂志》2012 年；129：1116-25。）
Background: The airway epithelium is the first line of defense against inhaled insults and therefore must be capable of coordinating appropriate inflammatory and immune responses. Objective: We sought to test the hypothesis that the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome, an intracellular danger-sensing complex, plays a critical role in airway epithelium-mediated immune responses to urban particulate matter (PM) exposure.Methods: In this study we (1) identified NLRP3 and caspase-1 expression in human airway epithelium bronchus and primary cells, (2) characterized NLRP3 inflammasome-mediated IL-1 beta production from human airway epithelium in response to PM, and (3) performed in vivo PM exposure experiments with wildtype and Nlrp3(-/-) mice.Results: Our results demonstrate that human airway epithelium contains a functional NLRP3 inflammasome that responds to PM exposure with caspase-1 cleavage and production of IL-1 beta. Exposure of Nlrp3(-/-) and wild-type mice to PM in vivo demonstrates NLRP3-dependent production of IL-1 beta in the lung, airway neutrophilia, and increases in CD11c(+hi)/MHC class II+hi cell numbers in intrathoracic lymph nodes.Conclusion: Our study is the first to characterize airway epithelial NLRP3 inflammasome-mediated immune responses to PM exposure, which might have implications in patients with asthma and other lung diseases. (J Allergy Clin Immunol 2012; 129:1116-25.)