Eurofins Lancaster Laboratories PSS, Winston-Salem, NC 27105, USA.
RAI Services Company, 401 North Main Street, Winston Salem, NC 27101, USA.
Toxicol In Vitro. 2019 Jun;57:117-125. doi: 10.1016/j.tiv.2019.02.012. Epub 2019 Feb 15.
Cigarette smoking exerts diverse physiological effects including immune suppression. To better characterize the biological effects of different categories of tobacco products, a genome-wide gene expression study was performed. Transcriptomic profiling was performed in PBMCs treated with different equi-nicotine units of aqueous extracts of cigarette smoke (termed Whole Smoke-Conditioned Medium, or WS-CM), or a single dose smokeless tobacco extract (STE) prepared from reference tobacco products. WS-CM induced dose-dependent changes in the expression of several genes. No significant expression differences between low WS-CM and media control were detected. However, transcripts were significantly affected by medium WS-CM (479), high WS-CM (2, 703), and STE (2, 156). The overlap between medium WS-CM and STE, and high WS-CM and STE, was minimal (34 and 65 transcripts, respectively). Hierarchical clustering revealed that gene expression profiles for STE and medium WS-CM co-clustered, while those affected by the high dose of WS-CM clustered distinctly. Functional analysis revealed that WS-CM, but not STE, uniquely affected genes involved in immune cell development and inflammatory response. Cascades of upstream regulators (e.g., TNF, IL1β, NFƙB) were identified for the observed gene expression changes and generally suppressed by WS-CM, but not by STE. Collectively, these findings demonstrate that combustible and non-combustible tobacco products elicit distinct biological effects, which could explain the observed chronic immune suppression in smokers.
吸烟会产生多种生理效应，包括免疫抑制。为了更好地描述不同类别的烟草产品的生物学效应，进行了一项全基因组基因表达研究。在 PBMC 中进行了转录组谱分析，这些细胞用不同等尼古丁单位的香烟烟雾的水提取物（称为全烟雾调理培养基，或 WS-CM）或来自参考烟草产品的单一剂量无烟烟草提取物（STE）处理。WS-CM 诱导了几个基因表达的剂量依赖性变化。低 WS-CM 和培养基对照之间没有检测到显著的表达差异。然而，中 WS-CM（479）、高 WS-CM（2,703）和 STE（2,156）显著影响了转录本。中 WS-CM 和 STE 之间以及高 WS-CM 和 STE 之间的重叠很小（分别为 34 和 65 个转录本）。层次聚类显示，STE 和中 WS-CM 的基因表达谱共同聚类，而受高剂量 WS-CM 影响的基因聚类则明显不同。功能分析表明，WS-CM 而不是 STE 独特地影响了与免疫细胞发育和炎症反应相关的基因。观察到的基因表达变化的上游调节剂级联（例如 TNF、IL1β、NFκB）被鉴定出来，并且通常被 WS-CM 而不是 STE 抑制。总的来说，这些发现表明可燃和不可燃的烟草产品会引起不同的生物学效应，这可以解释吸烟者中观察到的慢性免疫抑制。
