The aryl hydrocarbon receptor (AhR) transcription factor is activated by polycyclic aromatic hydrocarbons (PAH) and other ligands. Activated AhR binds to dioxin responsive elements (DRE) and initiates transcription of target genes, including the gene encoding prostaglandin endoperoxide synthase 2 (PTGS-2), which is also activated by the transcription factor NF-ĸB. PTGS-2 catalyzes the conversion of arachidonic acid (AA) into prostaglandins, thromboxanes or isoprostanes. 15-F2t-Isoprostane (IsoP), regarded as a universal marker of lipid peroxidation, is also induced by PAH exposure. We investigated the processes associated with lipid peroxidation in human alveolar basal epithelial cells (A549) exposed for 4 h or 24 h to model PAH (benzo[a]pyrene, BaP; 3-nitrobenzanthrone, 3-NBA) and organic extracts from ambient air particulate matter (EOM), collected in two seasons in a polluted locality. Both EOM induced the expression of CYP1A1 and CYP1B1; 24 h treatment significantly reduced PTGS-2 expression. IsoP levels decreased after both exposure periods, while the concentration of AA was not affected. The effects induced by BaP were similar to EOM except for increased IsoP levels after 4 h exposure and elevated AA concentration after 24 h treatment. In contrast, 3-NBA treatment did not induce CYP expression, had a weak effect on PTGS-2 expression, and, similar to BaP, induced IsoP levels after 4 h exposure and AA levels after 24 h treatment. All tested compounds induced the activity of NF-ĸB after the longer exposure period. In summary, our data suggest that EOM, and partly BaP, reduce lipid peroxidation by a mechanism that involves AhR-dependent inhibition of PTGS-2 expression. The effect of 3-NBA on IsoP levels is probably mediated by a different mechanism independent of AhR activation.

芳烃受体 (AhR) 转录因子由多环芳烃 (PAH) 和其他配体激活。激活的 AhR 与二恶英反应元件 (DRE) 结合并启动靶基因的转录，包括编码前列腺素内过氧化物合酶 2 (PTGS-2) 的基因，该基因也被转录因子 NF-ĸB 激活。PTGS-2 催化花生四烯酸 (AA) 转化为前列腺素、血栓烷或异前列腺素。15-F2t-异前列烷 (IsoP) 被认为是脂质过氧化的通用标志物，也会由 PAH 暴露诱导。我们研究了暴露于模型 PAH（苯并 [ a]芘，BaP；3-硝基苯并蒽酮 (3-NBA) 和来自环境空气颗粒物 (EOM) 的有机提取物，在污染地区两个季节收集。EOM均诱​​导CYP1A1和CYP1B1的表达；24 小时处理显着降低了 PTGS-2 表达。IsoP 水平在两个暴露期后均下降，而 AA 的浓度不受影响。除了暴露 4 小时后 IsoP 水平升高和 24 小时处理后 AA 浓度升高外，BaP 诱导的效果与 EOM 相似。相比之下，3-NBA 处理不诱导 CYP 表达，对 PTGS-2 表达的影响较弱，并且与 BaP 类似，在暴露 4 小时后诱导 IsoP 水平，在处理 24 小时后诱导 AA 水平。所有测试的化合物在较长的暴露期后都诱导了 NF-ĸB 的活性。总之，我们的数据表明 EOM 和部分 BaP，通过涉及 AhR 依赖性抑制 PTGS-2 表达的机制减少脂质过氧化。3-NBA 对 IsoP 水平的影响可能是由独立于 AhR 激活的不同机制介导的。