Singh Dhirendra Pratap, Begum Rizwana, Kaur Gagandeep, Bagam Prathyusha, Kambiranda Devaiah, Singh Rakesh, Batra Sanjay
Laboratory of Pulmonary Immunotoxicology, Department of Environmental Toxicology, 129 Health Research Center, Southern University and A&M College, Baton Rouge, LA, 70813, USA.
Southern University Agriculture Research and Extension Center, Southern University and A&M College, Baton Rouge, LA, 70813, USA.
Cell Biol Toxicol. 2021 Oct;37(5):773-793. doi: 10.1007/s10565-020-09573-x. Epub 2021 Jan 20.
Electronic cigarettes (e-cigs) are battery-operated heating devices that aerosolize e-liquid, typically containing nicotine and several other chemicals, which is then inhaled by a user. Over the past decade, e-cigs have gained immense popularity among both smokers and non-smokers. One reason for this is that they are advertised as a safe alternative to conventional cigarettes. However, the recent reports of e-cig use associated lung injury have ignited a considerable debate about the relative harm and benefits of e-cigs. The number of reports about e-cig-induced inflammation and pulmonary health is increasing as researchers seek to better understand the effects of vaping on human health. In line with this, we investigated the molecular events responsible for the e-cig vapor condensate (ECVC)-mediated inflammation in human lung adenocarcinoma type II epithelial cells (A549). In an attempt to limit the variables caused by longer ingredient lists of flavored e-cigs, tobacco-flavored ECVC (TF-ECVC±nicotine) was employed for this study. Interestingly, we observed significant upregulation of cytokines and chemokines (IL-6, IL-8, and MCP-1) in A549 cells following a 48 h TF-ECVC challenge. Furthermore, there was a significant increase in the expression of pattern recognition receptors TLR-4 and NOD-1, lipid raft-associated protein caveolin-1, and transcription factor NF-кB in TF-ECVC with and/or without nicotine-challenged lung epithelial cells. Our results further demonstrate the harboring of TLR-4 and NOD-1 in the caveolae of TF-ECVC-challenged A549 cells. Proteomic and lipidomic analyses of lipid raft fractions from control and challenged cells revealed a distinct protein and lipid profile in TF-ECVC (w/wo nicotine)-exposed A549 cells. Interestingly, the inflammatory effects of TF-ECVC (w/wo nicotine) were inhibited following the caveolin-1 knockdown, thus demonstrating a critical role of caveolae raft-mediated signaling in eliciting inflammatory responses upon TF-ECVC challenge. Graphical Abstract Graphical Abstract.
电子烟是一种由电池供电的加热装置，它能将电子烟液雾化，电子烟液通常含有尼古丁和其他几种化学物质，然后由使用者吸入。在过去十年中，电子烟在吸烟者和非吸烟者中都非常受欢迎。原因之一是它们被宣传为传统香烟的安全替代品。然而，最近关于使用电子烟导致肺部损伤的报道引发了一场关于电子烟相对危害和益处的激烈辩论。随着研究人员试图更好地了解吸电子烟对人类健康的影响，关于电子烟引起的炎症和肺部健康的报道数量正在增加。与此一致，我们研究了导致电子烟蒸汽冷凝物（ECVC）介导的人肺腺癌II型上皮细胞（A549）炎症的分子事件。为了限制由口味电子烟较长成分列表引起的变量，本研究采用了烟草味的ECVC（TF-ECVC±尼古丁）。有趣的是，在48小时的TF-ECVC刺激后，我们观察到A549细胞中细胞因子和趋化因子（IL-6、IL-8和MCP-1）显著上调。此外，在有和/或没有尼古丁刺激的肺上皮细胞中，TF-ECVC中模式识别受体TLR-4和NOD-1、脂筏相关蛋白小窝蛋白-1以及转录因子NF-κB的表达显著增加。我们的结果进一步证明了在TF-ECVC刺激的A549细胞的小窝中存在TLR-4和NOD-1。对对照细胞和受刺激细胞的脂筏部分进行蛋白质组学和脂质组学分析，揭示了TF-ECVC（含/不含尼古丁）处理的A549细胞中独特的蛋白质和脂质谱。有趣的是，在小窝蛋白-1敲低后，TF-ECVC（含/不含尼古丁）的炎症作用受到抑制，从而证明了小窝筏介导的信号在TF-ECVC刺激后引发炎症反应中的关键作用。图形摘要 图形摘要。
