Diesel exhaust alters the response of cultured primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD) to non-typeable Haemophilus influenzae.
Diesel exhaust alters the response of cultured primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD) to non-typeable Haemophilus influenzae.
复制标题
柴油排气改变了慢性阻塞性肺疾病（COPD）患者对不可抑制流感的培养的原发支气管上皮细胞的反应。
DOI：
10.1186/s12931-017-0510-4
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发表时间：
2017-01-28
影响因子：
5.8
通讯作者：
Kooter IM
中科院分区：
文献类型：
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作者：
Zarcone MC;van Schadewijk A;Duistermaat E;Hiemstra PS;Kooter IM
急性加重是慢性阻塞性肺疾病（COPD）患者发病和死亡的主要原因。已知细菌感染，如无法分型的流感嗜血杆菌感染（NTHi），以及暴露于柴油发动机排放物会导致COPD患者病情加重。然而，柴油废气（DE）暴露对上皮细胞对微生物刺激反应的影响尚不完全清楚，COPD患者和对照组上皮细胞对DE的反应可能存在差异，尚未研究。原代支气管上皮细胞（PBEC）来自年龄匹配的COPD患者（n = 7）和对照组（n = 5）。在气液界面（ALI）培养PBEC，实现粘膜纤毛分化。ALI-PBECs顶部暴露于新鲜生成的全DE或空气流中1小时。暴露后，在存在或不存在紫外线灭活的NTHi的情况下孵育3小时，然后分析上皮基因表达。DE单独诱导COPD患者和对照组细胞中氧化应激标志物（HMOX1, 50 - 100倍）和综合应激反应标志物（CHOP， 1.5- 2倍和GADD34, 1.5倍）的增加。COPD培养物暴露于DE后，NTHi导致GADD34表达增加（高达3倍）。重要的是，DE抑制了nthi诱导的抗菌肽S100A7和伴侣蛋白HSP5A/BiP的表达。我们的研究结果表明，在COPD供者和对照细胞中，分化的原代气道上皮细胞暴露于DE会导致HMOX1基因表达和综合应激反应标志物的激活，其程度相似。此外，DE进一步增加了nthi诱导的GADD34的表达，表明可能增强了综合应激反应。DE降低了nthi诱导的S100A7的表达。这些数据表明，暴露于DE可通过降低宿主对感染的防御能力和调节应激反应，在一定程度上对健康造成不利影响。本文的在线版本（doi:10.1186/s12931-017-0510-4）包含补充材料，可供授权用户使用。
Exacerbations constitute a major cause of morbidity and mortality in patients suffering from chronic obstructive pulmonary disease (COPD). Both bacterial infections, such as those with non-typeable Haemophilus influenzae (NTHi), and exposures to diesel engine emissions are known to contribute to exacerbations in COPD patients. However, the effect of diesel exhaust (DE) exposure on the epithelial response to microbial stimulation is incompletely understood, and possible differences in the response to DE of epithelial cells from COPD patients and controls have not been studied. Primary bronchial epithelial cells (PBEC) were obtained from age-matched COPD patients (n = 7) and controls (n = 5). PBEC were cultured at the air-liquid interface (ALI) to achieve mucociliary differentiation. ALI-PBECs were apically exposed for 1 h to a stream of freshly generated whole DE or air. Exposure was followed by 3 h incubation in presence or absence of UV-inactivated NTHi before analysis of epithelial gene expression. DE alone induced an increase in markers of oxidative stress (HMOX1, 50–100-fold) and of the integrated stress response (CHOP, 1.5–2-fold and GADD34, 1.5-fold) in cells from both COPD patients and controls. Exposure of COPD cultures to DE followed by NTHi caused an additive increase in GADD34 expression (up to 3-fold). Importantly, DE caused an inhibition of the NTHi-induced expression of the antimicrobial peptide S100A7, and of the chaperone protein HSP5A/BiP. Our findings show that DE exposure of differentiated primary airway epithelial cells causes activation of the gene expression of HMOX1 and markers of integrated stress response to a similar extent in cells from COPD donors and controls. Furthermore, DE further increased the NTHi-induced expression of GADD34, indicating a possible enhancement of the integrated stress response. DE reduced the NTHi-induced expression of S100A7. These data suggest that DE exposure may cause adverse health effects in part by decreasing host defense against infection and by modulating stress responses. The online version of this article (doi:10.1186/s12931-017-0510-4) contains supplementary material, which is available to authorized users.