PDF(Pubmed)
Abstract：
Cigarette smoking is a risk factor for several diseases such as cancer, cardiovascular disease (CVD), and chronic obstructive pulmonary diseases (COPD), however, the underlying mechanisms are not fully understood. Alternative nicotine products with reduced risk potential (RRPs) including tobacco heating products (THPs), and e-cigarettes have recently emerged as viable alternatives to cigarettes that may contribute to the overall strategy of tobacco harm reduction due to the significantly lower levels of toxicants in these products\' emissions as compared to cigarette smoke. Assessing the effects of RRPs on biological responses is important to demonstrate the potential value of RRPs towards tobacco harm reduction. Here, we evaluated the inflammatory and signaling responses of human lung epithelial cells to aqueous aerosol extracts (AqE) generated from the 1R6F reference cigarette, the glo™ THP, and the Vype ePen 3.0 e-cigarette using multiplex analysis of 37 inflammatory and phosphoprotein markers. Cellular exposure to the different RRPs and 1R6F AqEs resulted in distinct response profiles with 1R6F being the most biologically active followed by glo™ and ePen 3.0. 1R6F activated stress-related and pro-survival markers c-JUN, CREB1, p38 MAPK and MEK1 and led to the release of IL-1α. glo™ activated MEK1 and decreased IL-1β levels, whilst ePen 3.0 affected IL-1β levels but had no effect on the signaling activity compared to untreated cells. Our results demonstrated the reduced biological effect of RRPs and suggest that targeted analysis of inflammatory and cell signaling mediators is a valuable tool for the routine assessment of RRPs.
摘要：
吸烟是癌症等几种疾病的危险因素，心血管疾病（CVD），和慢性阻塞性肺疾病（COPD），然而,潜在的机制还没有完全理解。具有降低潜在风险（RRP）的替代尼古丁产品，包括烟草加热产品（THP），和电子香烟最近已经成为可行的替代品，香烟，可能有助于烟草危害减少的整体战略，由于显着降低水平的有毒物质在这些产品的排放相比，香烟烟雾。评估RRP对生物反应的影响对于证明RRP对减少烟草危害的潜在价值很重要。这里,我们评估了人肺上皮细胞对1R6F参考香烟产生的水性气溶胶提取物（AqE）的炎症和信号反应，glo™THP,和Vypeepen3.0电子烟使用37种炎症和磷蛋白标志物的多重分析。细胞暴露于不同的RRP和1R6FAqE导致不同的反应谱,其中1R6F是最具生物活性的,其次是glo™和ePen3.0。1R6F激活应激相关和促生存标志物c-JUN，CREB1、p38MAPK和MEK1导致IL-1α的释放。glo™激活MEK1并降低IL-1β水平，虽然epen3.0影响IL-1β水平，但与未处理的细胞相比，对信号活性没有影响。我们的结果表明RRP的生物学效应降低，并表明炎症和细胞信号传导介质的靶向分析是RRP常规评估的有价值的工具。
