Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China; Department of Respiratory Medicine, The No.1 Hospital of Shijiazhuang, Hebei, 050000, China.
Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China.
Ecotoxicol Environ Saf. 2020 Jun 1;195:110491. doi: 10.1016/j.ecoenv.2020.110491. Epub 2020 Mar 23.
Epidemiological studies have reported short-term fine particulate matter (PM2.5) exposure to increase incidence of asthma, related to the increase of airway hyperresponsiveness (AHR); however, the underlying mechanism remains unclear. Aim of this study was to elucidate the role of kallikrein in PM2.5-induced airway hyperresponsiveness and understand the underlying mechanism. Nose-only PM2.5 exposure system was used to generate a mouse model of airway hyperresponsiveness. Compared with the control group, PM2.5 exposure could significantly increase airway resistance, lung inflammation, kallikrein expression of bronchi-lung tissue and bradykinin (BK) secretion. However, these changes could be alleviated by kallikrein inhibitor. In addition，PM2.5 could increase the viability of human airway smooth muscle cells (hASMCs), accompanied by increased expression of kallikrein 14 (Klk14), bradykinin 2 receptor (B2R), bradykinin secretion and cytosol calcium level, while kallikrein 14 gene knockdown could significantly amelioratethe above response induced by PM2.5. Taken together, the data suggested kallikrein to play a key role in PM2.5-induced airway hyperresponsiveness, and that it could be a potential therapeutic target in asthma.
流行病学研究报告称，短期细颗粒物（PM2.5）暴露会增加哮喘发病率，与气道高反应性（AHR）增加有关；然而，其潜在机制尚不清楚。本研究旨在阐明激肽释放酶在 PM2.5 诱导的气道高反应性中的作用，并了解其潜在机制。使用仅鼻腔暴露 PM2.5 的系统生成了气道高反应性的小鼠模型。与对照组相比，PM2.5 暴露可显著增加气道阻力、肺炎症、支气管-肺组织中激肽释放酶的表达和缓激肽（BK）的分泌。然而，这些变化可以通过激肽释放酶抑制剂来缓解。此外，PM2.5 可增加人气道平滑肌细胞（hASMCs）的活力，同时激肽释放酶 14（Klk14）、缓激肽 2 受体（B2R）、缓激肽分泌和细胞浆钙水平表达增加，而激肽释放酶 14 基因敲低可显著减轻 PM2.5 诱导的上述反应。综上所述，数据表明激肽释放酶在 PM2.5 诱导的气道高反应性中起关键作用，它可能是哮喘的潜在治疗靶点。
