Abstract:Acute exposure to as little as three cigarettes and chronic smoking induce largely concordant changes in airway epithelial gene expression. Differences in short-term and long-term effects of smoking on metallothionein expression and their relationship to lung cancer requires further study given these enzymes' role in the oxidative stress response.
“…Thus, these results suggest that the effect of cigarette smoking on expression of ACE2, TMPRSS2, and cathepsin L is more likely an acute reaction than a chronic alteration of the tissue. The acute effect of cigarette smoking on ACE2 was confirmed in a further dataset (47). In this study, current smokers were asked to refrain from cigarette smoking for at least 2 days and then subjected to acute smoking exposure.…”
Section: Expression Of Ace2 Tmprss2 and Cathepsin L In Never Smokermentioning
SARS-CoV-2 enters into human airway epithelial cells via membrane fusion or endocytosis, and this process is dependent on ACE2, TMPRSS2, and cathepsin L. In this study, we examined the expression profiles of the three SARS-CoV-2 entry genes in primary human airway epithelial cells isolated from smokers, non-smokers, patients with chronic obstructive pulmonary disease or lung cancer. An exhaustive search of the GEO database was performed to identify eligible data on 1st June 2020. In total, 46 GEO datasets comprising transcriptomic data of 3,053 samples were identified as eligible data for further analysis. All meta-analysis were performed using RStudio. Standardized mean difference was utilized to assess the effect size of a factor on the expression of targeted genes and 95% confidence intervals (CIs) were calculated. This study revealed that (i) cigarette smoking is associated with an increased expression of ACE2 and TMPRSS2 and a decreased expression of cathepsin L; (ii) significant alternations in expression of ACE2, TMPRSS2, and cathepsin L were observed between current smokers and former smokers, but not between former smokers and never smokers; (iii) when compared with healthy controls with identical smoking status, patients with COPD or lung cancer showed negligible changes in expression of ACE2, TMPRSS2, and cathepsin L. Therefore, this study implicates cigarette smoking might contribute to the development of COVID-19 by affecting the expression of SARS-CoV-2 entry genes, while smoking cessation could be effective to reduce the potential risk.
“…Thus, these results suggest that the effect of cigarette smoking on expression of ACE2, TMPRSS2, and cathepsin L is more likely an acute reaction than a chronic alteration of the tissue. The acute effect of cigarette smoking on ACE2 was confirmed in a further dataset (47). In this study, current smokers were asked to refrain from cigarette smoking for at least 2 days and then subjected to acute smoking exposure.…”
Section: Expression Of Ace2 Tmprss2 and Cathepsin L In Never Smokermentioning
SARS-CoV-2 enters into human airway epithelial cells via membrane fusion or endocytosis, and this process is dependent on ACE2, TMPRSS2, and cathepsin L. In this study, we examined the expression profiles of the three SARS-CoV-2 entry genes in primary human airway epithelial cells isolated from smokers, non-smokers, patients with chronic obstructive pulmonary disease or lung cancer. An exhaustive search of the GEO database was performed to identify eligible data on 1st June 2020. In total, 46 GEO datasets comprising transcriptomic data of 3,053 samples were identified as eligible data for further analysis. All meta-analysis were performed using RStudio. Standardized mean difference was utilized to assess the effect size of a factor on the expression of targeted genes and 95% confidence intervals (CIs) were calculated. This study revealed that (i) cigarette smoking is associated with an increased expression of ACE2 and TMPRSS2 and a decreased expression of cathepsin L; (ii) significant alternations in expression of ACE2, TMPRSS2, and cathepsin L were observed between current smokers and former smokers, but not between former smokers and never smokers; (iii) when compared with healthy controls with identical smoking status, patients with COPD or lung cancer showed negligible changes in expression of ACE2, TMPRSS2, and cathepsin L. Therefore, this study implicates cigarette smoking might contribute to the development of COVID-19 by affecting the expression of SARS-CoV-2 entry genes, while smoking cessation could be effective to reduce the potential risk.
“…The transcriptomics analysis revealed several IEGs common to all exposures, as well as gene expression profiles that characterise each type of exposure, thereby indicating the specificity of the genetic response. Contrary to the immune suppression experienced in the lungs following chronic exposure, the function of common IEGs are, in most cases, transmembrane receptor mediators of immune response, similar to the known physiological and genetic changes observed after acute exposure to CS 106 136 137. The group of common novel IEGs were found to be strongly associated with B cell immunity.…”
ObjectiveWe investigated the effects of chronic waterpipe (WP) smoke on pulmonary function and immune response in a murine model using a research-grade WP and the effects of acute exposure on the regulation of immediate-early genes (IEGs).MethodsWP smoke was generated using three WP smoke puffing regimens based on the Beirut regimen. WP smoke samples generated under these puffing regimens were quantified for nicotine concentration. Mice were chronically exposed for 6 months followed by assessment of pulmonary function and airway inflammation. Transcriptomic analysis using RNAseq was conducted after acute exposure to characterise the IEG response. These biomarkers were then compared with those generated after exposure to dry smoke (without water added to the WP bowl).ResultsWe determined that nicotine composition in WP smoke ranged from 0.4 to 2.5 mg per puffing session. The lung immune response was sensitive to the incremental severity of chronic exposure, with modest decreases in airway inflammatory cells and chemokine levels compared with air-exposed controls. Pulmonary function was unmodified by chronic WP exposure. Acute WP exposure was found to activate the immune response and identified known and novel IEG as potential biomarkers of WP exposure.ConclusionChronic exposure to WP smoke leads to immune suppression without significant changes to pulmonary function. Transcriptomic analysis of the lung after acute exposure to WP smoke showed activation of the immune response and revealed IEGs that are common to WP and dry smoke, as well as pools of IEGs unique to each exposure, identifying potential biomarkers specific to WP exposure.
“…BNIP3 gene is an important regulator during long-term nicotine-induced cell death in several cell types (Erkan et al., 2005, Tang et al., 2007). Metallothionein family genes play a role in the protection against metal toxicity and oxidative stress, and have been shown to be suppressed in chronic smokers (Billatos et al., 2018). These genes are involved in apoptosis, ROS generation, mitochondrial function, and response to metal ion pathways (Figure 2C), indicating that EBs have poor cell survival upon nicotine exposure.Figure 2Nicotine Exposure Induces Cell-Type-Specific Response(A) Cell proportion fluctuation for each cell type with nicotine exposure.…”
Summary
Nicotine, the main chemical constituent of tobacco, is highly detrimental to the developing fetus by increasing the risk of gestational complications and organ disorders. The effects of nicotine on human embryonic development and related mechanisms, however, remain poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) of human embryonic stem cell (hESC)-derived embryoid body (EB) in the presence or absence of nicotine. Nicotine-induced lineage-specific responses and dysregulated cell-to-cell communication in EBs, shedding light on the adverse effects of nicotine on human embryonic development. In addition, nicotine reduced cell viability, increased reactive oxygen species (ROS), and altered cell cycling in EBs. Abnormal Ca
2+
signaling was found in muscle cells upon nicotine exposure, as verified in hESC-derived cardiomyocytes. Consequently, our scRNA-seq data suggest direct adverse effects of nicotine on hESC differentiation at the single-cell level and offer a new method for evaluating drug and environmental toxicity on human embryonic development
in utero
.
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