Bosson Jenny, Blomberg Anders, Pourazar Jamshid, Mudway Ian S, Frew Anthony J, Kelly Frank J, Sandström Thomas
Department of Respiratory Medicine and Allergy, University Hospital, Umeå, Sweden.
Inhal Toxicol. 2009 Sep;21(11):913-9. doi: 10.1080/08958370802657389.
Exposure to elevated concentrations of ozone, a common air pollutant, has been associated with numerous adverse health effects. We have previously reported the time-course of ozone-induced airway inflammation, demonstrating an early up-regulation of vascular endothelial adhesion molecules in bronchial mucosa at 1.5 hours, followed by a neutrophilic infiltration 6 hours after exposure to 0.2 ppm ozone. We hypothesized that the neutrophilic infiltration in the bronchial mucosa would reflect an early increase in bronchial epithelial expression of redox-sensitive transcription factors and kinases regulating neutrophil chemoattractant expression. To test this hypothesis, endobronchial biopsies were obtained from healthy human subjects (n = 11) 1.5 hours after 0.2 ppm of ozone and filtered air exposures (lasting for 2 hours) and stained for mitogen-activated protein kinases (MAPKs), transcription factors, and neutrophil chemoattractants. Total epithelial staining was quantified, as well as the extent of nuclear translocation. Contrary to expectation, ozone significantly suppressed total and nuclear expression of nuclear factor kappaB (NFkappaB) in bronchial epithelial cells (p = 0.02 and p = 0.003 respectively). Similarly, the total staining for phosphorylated C-jun was suppressed (p = 0.021). Expression of interleukin 8 (IL-8) in the bronchial epithelium was likewise decreased after ozone (p = 0.018), while GRO-alpha, ENA-78, C-fos, p-p38, p-JNK, and p-ERK stainings were unchanged. These data suggest that the redox-sensitive NFkappaB and activator protein 1 (AP-1) pathways within the human bronchial epithelium do not seem to be involved in the early inflammatory cell recruitment pathways in healthy subjects exposed to ozone.
暴露于高浓度的臭氧（一种常见的空气污染物）已与众多不良健康影响相关联。我们之前曾报道过臭氧诱导气道炎症的时间进程，表明在暴露于0.2 ppm臭氧1.5小时后支气管黏膜中血管内皮黏附分子早期上调，随后在暴露6小时后出现中性粒细胞浸润。我们推测支气管黏膜中的中性粒细胞浸润将反映支气管上皮中调节中性粒细胞趋化因子表达的氧化还原敏感转录因子和激酶的早期增加。为了验证这一假设，在健康人类受试者（n = 11）暴露于0.2 ppm臭氧和过滤空气（持续2小时）1.5小时后获取支气管活检组织，并对丝裂原活化蛋白激酶（MAPK）、转录因子和中性粒细胞趋化因子进行染色。对上皮细胞的总染色以及核转位程度进行了定量分析。与预期相反，臭氧显著抑制了支气管上皮细胞中核因子κB（NFκB）的总表达和核表达（分别为p = 0.02和p = 0.003）。同样，磷酸化C-jun的总染色也受到抑制（p = 0.021）。臭氧处理后支气管上皮中白细胞介素8（IL-8）的表达同样降低（p = 0.018），而生长调节致癌基因α（GRO-α）、上皮中性粒细胞激活肽78（ENA-78）、C-fos、磷酸化p38、磷酸化JNK和磷酸化ERK的染色未发生变化。这些数据表明，在暴露于臭氧的健康受试者中，人支气管上皮内的氧化还原敏感NFκB和激活蛋白1（AP-1）途径似乎未参与早期炎症细胞募集途径。
