Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Triskelion B.V., Zeist, The Netherlands.
Toxicol In Vitro. 2018 Apr;48:221-231. doi: 10.1016/j.tiv.2018.01.024.
Harmful effects of diesel emissions can be investigated via exposures of human epithelial cells, but most of previous studies have largely focused on the use of diesel particles or emission sources that are poorly representative of engines used in current traffic. We studied the cellular response of primary bronchial epithelial cells (PBECs) at the air-liquid interface (ALI) to the exposure to whole diesel exhaust (DE) generated by a Euro V bus engine, followed by treatment with UV-inactivated non-typeable Haemophilus influenzae (NTHi) bacteria to mimic microbial exposure. The effect of prolonged exposures was investigated, as well as the difference in the responses of cells from COPD and control donors and the effect of emissions generated during a cold start. HMOX1 and NQO1 expression was transiently induced after DE exposure. DE inhibited the NTHi-induced expression of human beta-defensin-2 (DEFB4A) and of the chaperone HSPA5/BiP. In contrast, expression of the stress-induced PPP1R15A/GADD34 and the chemokine CXCL8 was increased in cells exposed to DE and NTHi. HMOX1 induction was significant in both COPD and controls, while inhibition of DEFB4A expression by DE was significant only in COPD cells. No significant differences were observed when comparing cellular responses to cold engine start and prewarmed engine emissions.
柴油排放的有害影响可通过人体上皮细胞暴露来进行研究，但以前的大多数研究主要集中在使用柴油颗粒或缺乏代表性的排放源上，而这些排放源与当前交通中使用的发动机不匹配。我们研究了在气液界面（ALI）暴露于由 Euro V 巴士发动机产生的全柴油废气（DE）后，原发性支气管上皮细胞（PBEC）的细胞反应，随后用紫外线灭活非定型流感嗜血杆菌（NTHi）细菌处理，以模拟微生物暴露。我们还研究了延长暴露的效果，以及 COPD 患者和对照供体细胞反应的差异，以及冷启动期间产生的排放物的影响。DE 暴露后 HMOX1 和 NQO1 的表达被短暂诱导。DE 抑制了 NTHi 诱导的人β防御素-2（DEFB4A）和伴侣蛋白 HSPA5/BiP 的表达。相比之下，暴露于 DE 和 NTHi 的细胞中应激诱导的 PPP1R15A/GADD34 和趋化因子 CXCL8 的表达增加。HMOX1 的诱导在 COPD 和对照组中均显著，而 DE 对 DEFB4A 表达的抑制仅在 COPD 细胞中显著。当比较冷启动发动机和预热发动机排放物对细胞反应的影响时，未观察到显著差异。
