Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, 02115, Massachusetts, USA.
Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
Sci Rep. 2019 Feb 1;9(1):1400. doi: 10.1038/s41598-018-37913-9.
The widespread use of electronic cigarettes (e-cigarettes or e-cig) is a growing public health concern. Diacetyl and its chemical cousin 2,3-pentanedione are commonly used to add flavors to e-cig; however, little is known about how the flavoring chemicals may impair lung function. Here we report that the flavoring chemicals induce transcriptomic changes and perturb cilia function in the airway epithelium. Using RNA-Seq, we identified a total of 163 and 568 differentially expressed genes in primary normal human bronchial epithelial (NHBE) cells that were exposed to diacetyl and 2,3-pentanedione, respectively. DAVID pathway analysis revealed an enrichment of cellular pathways involved in cytoskeletal and cilia processes among the set of common genes (142 genes) perturbed by both diacetyl and 2,3-pentanedione. Consistent with this, qRT-PCR confirmed that the expression of multiple genes involved in cilia biogenesis was significantly downregulated by diacetyl and 2,3-pentanedione in NHBE cells. Furthermore, immunofluorescence staining showed that the number of ciliated cells was significantly decreased by the flavoring chemicals. Our study indicates that the two widely used e-cig flavoring chemicals impair the cilia function in airway epithelium and likely contribute to the adverse effects of e-cig in the lung.
电子烟（电子香烟或电子雾化器）的广泛使用是一个日益严重的公共卫生问题。双乙酰及其化学同类物 2,3-戊二酮常用于为电子烟添加风味；然而，人们对调味化学品如何损害肺功能知之甚少。在这里，我们报告称，调味化学品会引起呼吸道上皮细胞的转录组变化和纤毛功能障碍。通过 RNA-Seq，我们在暴露于双乙酰和 2,3-戊二酮的原代正常人类支气管上皮 (NHBE) 细胞中分别鉴定出总共 163 和 568 个差异表达基因。DAVID 途径分析显示，在双乙酰和 2,3-戊二酮共同干扰的一组常见基因（142 个基因）中，细胞骨架和纤毛过程相关的细胞途径富集。与此一致，qRT-PCR 证实双乙酰和 2,3-戊二酮显著下调了 NHBE 细胞中多个参与纤毛发生的基因的表达。此外，免疫荧光染色显示，这些风味化学物质显著减少了有纤毛的细胞数量。我们的研究表明，两种广泛使用的电子烟调味化学品会损害呼吸道上皮细胞的纤毛功能，并可能导致电子烟对肺部的不良影响。
