Ambient fine particulate matter of <2.5 μm (PM2.5) has been linked to morbidity and mortality from respiratory and cardiovascular diseases. Lung epithelial cells bear the brunt of PM2.5 exposure. In the present study, we found that exposure of A549 cells to the water‐soluble fraction of PM2.5 (WS‐PM2.5) promoted the expression and internalization of caveolin‐1. Caveolin‐1 knockdown restrained the endocytosis of WS‐PM2.5. In addition, WS‐PM2.5 accumulation in the cells induced the phosphorylation of serine/threonine protein kinase B (AKT) and nuclear factor κ‐light‐chain enhancer of activated B cells (NFκB), as well as the expression of Krüppel‐like factor 5 (KLF5). Inhibiting activation of AKT and NFκB also partly reduced WS‐PM2.5 concentration in cells, but KLF5 knockdown did not affect the intracellular accumulation of WS‐PM2.5. KLF5 knockdown suppressed cytochrome P450 family 1 subfamily A member 1 (CYP1A1) expression and activated caspase 3. Luciferase reporter assay and chromatin immunoprecipitation assay showed that KLF5 positively regulated the transcription of KLF5. These results suggested that caveolin‐1 was required for the endocytosis of WS‐PM2.5. Intracellular accumulation of WS‐PM2.5 activated AKT and NFκB, which facilitated WS‐PM2.5 endocytosis. WS‐PM2.5 accumulation also induced KLF5 expression, increasing the transcriptional expression of CYP1A1, which contributed to activate caspase 3.

中文翻译：

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<2.5μm的颗粒物的水溶性部分通过调节小窝蛋白1和Krüppel样因子5的表达促进肺上皮细胞凋亡

<2.5μm（PM2.5）的环境细颗粒物与呼吸系统疾病和心血管疾病的发病率和死亡率有关。肺上皮细胞首当其冲暴露于PM2.5。在本研究中，我们发现A549细胞暴露于PM2.5的水溶性部分（WS-PM2.5）促进了Caveolin-1的表达和内在化。Caveolin-1组合式抑制了WS-PM2.5的内吞作用。此外，WS-PM2.5在细胞中的积累诱导了丝氨酸/苏氨酸蛋白激酶B（AKT）的磷酸化和活化B细胞的核因子κ轻链增强子（NFκB）的表达以及Krüppel-像因子5（KLF5）。抑制AKT和NFκB的活化也可以部分降低细胞中WS-PM2.5的浓度，但是KLF5的敲低并不影响WS-PM2.5的细胞内积累。KLF5敲低抑制细胞色素P450家族1亚家族A成员1（CYP1A1）的表达并激活caspase3。荧光素酶报告基因测定和染色质免疫沉淀测定表明KLF5积极调节KLF5的转录。这些结果表明，WS-PM2.5的胞吞作用需要小窝蛋白-1。WS-PM2.5的细胞内积累激活了AKT和NFκB，从而促进了WS-PM2.5的内吞作用。WS-PM2.5的积累也诱导KLF5表达，增加CYP1A1的转录表达，这有助于激活caspase 3。这些结果表明，WS-PM2.5的胞吞作用需要小窝蛋白-1。WS-PM2.5的细胞内积累激活了AKT和NFκB，从而促进了WS-PM2.5的内吞作用。WS-PM2.5的积累也诱导KLF5表达，增加CYP1A1的转录表达，这有助于激活caspase 3。这些结果表明，WS-PM2.5的胞吞作用需要小窝蛋白-1。WS-PM2.5的细胞内积累激活了AKT和NFκB，从而促进了WS-PM2.5的内吞作用。WS-PM2.5的积累也诱导KLF5表达，增加CYP1A1的转录表达，这有助于激活caspase 3。