Traffic-derived particles are important contributors to the adverse health effects of ambient particulate matter (PM). In Nordic countries, mineral particles from road pavement and diesel exhaust particles (DEP) are important constituents of traffic-derived PM. In the present study we compared the pro-inflammatory responses of mineral particles and DEP to PM from two road tunnels, and examined the mechanisms involved. The pro-inflammatory potential of 100 µg/mL coarse (PM10-2.5), fine (PM2.5-0.18) and ultrafine PM (PM0.18) sampled in two road tunnels paved with different stone materials was assessed in human bronchial epithelial cells (HBEC3-KT), and compared to DEP and particles derived from the respective stone materials. Release of pro-inflammatory cytokines (CXCL8, IL-1α, IL-1β) was measured by ELISA, while the expression of genes related to inflammation (COX2, CXCL8, IL-1α, IL-1β, TNF-α), redox responses (HO-1) and metabolism (CYP1A1, CYP1B1, PAI-2) was determined by qPCR. The roles of the aryl hydrocarbon receptor (AhR) and reactive oxygen species (ROS) were examined by treatment with the AhR-inhibitor CH223191 and the anti-oxidant N-acetyl cysteine (NAC). Road tunnel PM caused time-dependent increases in expression of CXCL8, COX2, IL-1α, IL-1β, TNF-α, COX2, PAI-2, CYP1A1, CYP1B1 and HO-1, with fine PM as more potent than coarse PM at early time-points. The stone particle samples and DEP induced lower cytokine release than all size-fractionated PM samples for one tunnel, and versus fine PM for the other tunnel. CH223191 partially reduced release and expression of IL-1α and CXCL8, and expression of COX2, for fine and coarse PM, depending on tunnel, response and time-point. Whereas expression of CYP1A1 was markedly reduced by CH223191, HO-1 expression was not affected. NAC reduced the release and expression of IL-1α and CXCL8, and COX2 expression, but augmented expression of CYP1A1 and HO-1. The results indicate that the pro-inflammatory responses of road tunnel PM in HBEC3-KT cells are not attributed to the mineral particles or DEP alone. The pro-inflammatory responses seem to involve AhR-dependent mechanisms, suggesting a role for organic constituents. ROS-mediated mechanisms were also involved, probably through AhR-independent pathways. DEP may be a contributor to the AhR-dependent responses, although other sources may be of importance.

中文翻译：

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不同机制在人细支气管上皮细胞中交通源性颗粒物引发的促炎症反应中的作用

交通产生的颗粒物是造成环境颗粒物 (PM) 不利健康影响的重要因素。在北欧国家，路面中的矿物颗粒和柴油机尾气颗粒 (DEP) 是交通产生的 PM 的重要组成部分。在本研究中，我们比较了两个公路隧道中矿物颗粒和 DEP 对 PM 的促炎反应，并检查了其中涉及的机制。在两条铺有不同石材的公路隧道中采样的 100 µg/mL 粗颗粒 (PM10-2.5)、细颗粒 (PM2.5-0.18) 和超细颗粒 PM (PM0.18) 对人支气管上皮细胞的促炎潜力进行了评估(HBEC3-KT)，并与 DEP 和源自各自石材的颗粒进行比较。通过ELISA测量促炎细胞因子（CXCL8、IL-1α、IL-1β）的释放，同时检测与炎症相关的基因（COX2、CXCL8、IL-1α、IL-1β、TNF-α）的表达、氧化还原反应（HO-1）和代谢（CYP1A1、CYP1B1、PAI-2）通过 qPCR 测定。通过使用 AhR 抑制剂 CH223191 和抗氧化剂 N-乙酰半胱氨酸 (NAC) 处理，检查芳烃受体 (AhR) 和活性氧 (ROS) 的作用。公路隧道 PM 引起 CXCL8、COX2、IL-1α、IL-1β、TNF-α、COX2、PAI-2、CYP1A1、CYP1B1 和 HO-1 表达的时间依赖性增加，细颗粒 PM 比粗颗粒 PM 更有效在早期时间点。对于一个隧道，石颗粒样本和 DEP 诱导的细胞因子释放低于所有尺寸分级的 PM 样本，而对于另一隧道，则与细颗粒 PM 相比。对于细颗粒物和粗颗粒物，CH223191 部分降低了 IL-1α 和 CXCL8 的释放和表达，以及 COX2 的表达，具体取决于隧道、响应和时间点。尽管 CH223191 显着降低了 CYP1A1 的表达，但 HO-1 的表达并未受到影响。NAC减少IL-1α和CXCL8以及COX2表达的释放和表达，但增加CYP1A1和HO-1的表达。结果表明，HBEC3-KT 细胞中公路隧道 PM 的促炎反应不仅仅归因于矿物颗粒或 DEP。促炎症反应似乎涉及 AhR 依赖性机制，表明有机成分的作用。ROS 介导的机制也参与其中，可能是通过 AhR 独立途径。DEP 可能是 AhR 依赖性反应的一个贡献者，尽管其他来源可能也很重要。