Effects Of Cigarette Smoke Extract Research Articles

Cigarette smoke extract decreases human bone marrow mesenchymal stromal cell adipogenic differentiation

BackgroundSmoking and nicotine impose detrimental health effects including adipose tissue dysfunction. Despite extensive physiological evidence, the cellular mechanisms remain poorly understood, with few studies examining the effects of cigarette smoke extract (CSE) or nicotine on adipocyte differentiation. MethodsPrimary human bone marrow-derived mesenchymal stromal cells (MSCs) were exposed to CSE or nicotine (50–500 ng/ml) during adipogenic differentiation. Cell viability and metabolic activity were assessed via MTT assay. Lipid droplet accumulation was evaluated using Sudan III staining and quantitative image analysis. Adiponectin, IL6, and IL8 concentrations were measured after 35 days using ELISA. ResultsAt these doses, CSE and nicotine do not immediately affect cell viability but inhibit undifferentiated cell proliferation. Notably, both agents at 50 ng/ml significantly increased lipid accumulation during adipogenesis, while higher CSE doses nearly completely inhibited this process. Additionally, CSE dose-dependently decreased adiponectin secretion and increased IL6 and IL8, indicating a shift towards an inflammatory state. Nicotine alone primarily increased IL6 secretion with less pronounced effects. ConclusionThe study highlights the complex impact of CSE and nicotine on adipocyte function during early differentiation from MSCs. Dose-dependent changes in lipid accumulation, cytokine, and adiponectin secretion induced by CSE and nicotine can partly explain smoking-related adipose tissue dysfunction.

Exploring the relationship between pyroptosis and inflammatory bone loss: Evidence from a cigarette smoke-induced osteoporosis mouse model

Smoking is by far one of the greatest public health threats and is recognized as an important predisposing factor for osteoporosis. Exposure to cigarette smoke (CS) has been reported to be associated with inflammation-associated diseases through the induction of pyroptosis. Nevertheless, the correlation between pyroptosis and bone loss induced by CS remains uninvestigated. Here, a mouse model of mainstream smoke exposure-induced osteoporosis was established. μCT, biomechanical testing, and immunohistochemical staining of bone tissue were used to assess the deleterious effects of CS on bone metabolism. In vitro, the effects of cigarette smoke extracts (CSE) on mouse primary bone marrow-derived mesenchymal stem cells (BMSCs) were tested by cell viability assays, gene and protein expression assays, and alizarin red staining. The utilization of the pyroptosis inhibitor MCC950 served to confirm the critical role of BMSCs pyroptosis in CS-induced osteoporosis. Our results indicated that exposure to mainstream smoke led to a notable decrease in the quantity of osteoblasts and hindered the process of osteogenic differentiation in mice. Additionally, there was a significant increase in the expression of pyroptosis-related proteins in the bone marrow. The inhibitory effects of CSE on cell viability and osteogenic differentiation of BMSCs were found to be dose-dependent in vitro. However, the presence of the pyroptosis inhibitor MCC950 significantly improved the impaired osteogenic differentiation and bone mineralization caused by CSE. These results highlight the crucial involvement of BMSCs pyroptosis in the development of bone loss induced by CS. In summary, the findings of this study provide novel evidence that CS exerts a detrimental effect on the process of osteogenesis in BMSCs through the induction of pyroptosis, ultimately leading to bone loss. Inhibition of pyroptosis effectively attenuated the toxicological effects of CS on BMSCs, providing a new target for preventing inflammatory osteoporosis.

Cigarette Smoke Constituents and Nicotine Differentially Affect Cytokine Production by Human Macrophages Stimulated by TLR Ligands In Vitro: Considerations for a Standardised Protocol.

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition associated with cigarette (tobacco) smoking. Numerous in vivo animal studies have been conducted to investigate the links between cigarette smoke, nicotine and infection in lung pathology. As an alternative to animal experiments, we used an in vitro system to investigate the effects of cigarette smoke extract (CSE) or nicotine on TNF-α and IL-10 production by monocyte-derived human macrophages. The macrophages were simultaneously stimulated with either poly-IC (as a chemical surrogate for viral infection) or lipopolysaccharide (as a chemical surrogate for Gram-negative bacterial infection). CSE enhanced TNF-α production, whereas nicotine inhibited IL-10 production by the macrophages, particularly when co-stimulated with the microbial chemical surrogates. A system of this type may help to further our understanding of the immunological and inflammatory effects of smoking, without recourse to in vivo studies. Requirements for the optimisation and standardisation of such an in vitro system are also discussed.

Direct toxicity of cigarette smoke extract on cardiac function mediated by mitochondrial dysfunction in Sprague-Dawley rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes.

Cigarette smoke has been recognized as a major risk factor for cardiovascular disease. However, its direct effects on rodent and human cardiomyocytes and its cellular mechanisms are not fully understood. In this study, we examined the direct effects of cigarette smoke extract (CSE) on contractile functions, intracellular Ca2+ dynamics, and mitochondrial function using cultured or freshly isolated rat ventricular myocytes and human induced pluripotent stem cell (iPS)-derived cardiomyocytes. In rat cardiomyocytes, CSE (≥0.1%) resulted in a time- and concentration-dependent cessation of spontaneous beating of cultured cardiomyocytes, eventually leading to cell death, which indicates direct toxicity. In addition, 1% CSE reduced contractile function of freshly isolated ventricular myocytes. Similar contractile dysfunction (declined spontaneous beating rate and contractility) was also observed in human iPS-derived cardiomyocytes. Regarding intracellular Ca2+ dynamics, 1% CSE increased the Ca2+ transient amplitude by greatly increasing systolic Ca2+ levels and slightly increasing diastolic Ca2+ levels. CSE also accelerated the decay of Ca2+ transients, and triggered spike-shaped Ca2+ transients in some cells. These results indicate that CSE causes abnormal Ca2+ dynamics in cardiomyocytes. Furthermore, CSE induced a cascade of mitochondrial dysfunctions, including increased mitochondrial reactive oxygen species, opening of mitochondrial permeability transition pore, reduction of mitochondrial membrane potential, and release of cytochrome c from mitochondria. These results suggest that CSE-induced contractile dysfunction and myocardial cell death is caused by abnormal Ca2+ dynamics and subsequent mitochondrial dysregulation, which would result in reduced bioenergetics and activation of cell death pathways.

Cigarette Smoke Extract Induces MUC5AC Expression Through the ROS/ IP3R/Ca2+ Pathway in Calu-3 Cells.

Chronic obstructive pulmonary disease (COPD) is caused by exposure to noxious external particles, air pollution, and the inhalation of cigarette smoke. Airway mucus hypersecretion particularly mucin5AC (MUC5AC), is a crucial pathological feature of COPD and is associated with its initiation and progression. In this study, we aimed to investigate the effects of cigarette smoke extract (CSE) on MUC5AC expression, particularly the mechanisms by which reactive oxygen species (ROS) induce MUC5AC expression. The effects of CSE on the expression of MUC5AC and mucin5B (MUC5B) were investigated in vitro in Calu-3 cells. MUC5AC and MUC5B expression levels were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). Total cellular levels of ROS and Ca2+ were determined using DCFH-DA and Fluo-4 AM. Subsequently, the expression levels of IP3R, IRE1α, p-IRE1α and XBP1s were measured by Western blotting. Gene silencing was achieved by using small-interfering RNAs. Our findings revealed that exposure to CSE increased MUC5AC levels and upregulated ROS, IP3R/Ca2+ and unfolded protein response (UPR)-associated factors. In addition, knockdown of IP3R using siRNA decreased CSE-induced Ca2+ production, UPR-associated factors, and MUC5AC expression. Furthermore, 10 mM N-acetyl-l-cysteine (NAC) treatment suppressed the effects of CSE, including ROS generation, IP3R/ Ca2+, UPR activation, and MUC5AC overexpression. Our results suggest that ROS regulates CSE-induced UPR and MUC5AC overexpression through IP3R/ Ca2+ signaling. Additionally, we identified NAC as a promising therapeutic agent for mitigating CSE-induced MUC5AC overexpression.

Formoterol Exerts Anti-Cancer Effects Modulating Oxidative Stress and Epithelial-Mesenchymal Transition Processes in Cigarette Smoke Extract Exposed Lung Adenocarcinoma Cells.

Lung cancer frequently affects patients with Chronic Obstructive Pulmonary Disease (COPD). Cigarette smoke (CS) fosters cancer progression by increasing oxidative stress and by modulating epithelial-mesenchymal transition (EMT) processes in cancer cells. Formoterol (FO), a long-acting β2-agonist widely used for the treatment of COPD, exerts antioxidant activities. This study explored in a lung adenocarcinoma cell line (A549) whether FO counteracted the effects of cigarette smoke extract (CSE) relative to oxidative stress, inflammation, EMT processes, and cell migration and proliferation. A549 was stimulated with CSE and FO, ROS were evaluated by flow-cytometry and by nanostructured electrochemical sensor, EMT markers were evaluated by flow-cytometry and Real-Time PCR, IL-8 was evaluated by ELISA, cell migration was assessed by scratch and phalloidin test, and cell proliferation was assessed by clonogenic assay. CSE significantly increased the production of ROS, IL-8 release, cell migration and proliferation, and SNAIL1 expression but significantly decreased E-cadherin expression. FO reverted all these phenomena in CSE-stimulated A549 cells. The present study provides intriguing evidence that FO may exert anti-cancer effects by reverting oxidative stress, inflammation, and EMT markers induced by CS. These findings must be validated in future clinical studies to support FO as a valuable add-on treatment for lung cancer management.

Cigarette Smoke Extract Contributes to the Inception and Aggravation of Asthmatic Inflammation by Stimulating Innate Immunity

Purpose: Smoking is a risk factor for the development of asthma and worsens the long-term prognosis of asthma. This study investigated the effect of cigarette smoke extract (CSE) on innate immune cells such as innate lymphoid cells (ILCs) and macrophages in a murine model of induced asthma. Methods: Six-week-old female BALB/C mice were exposed to ovalbumin (OVA) via an intranasal route with or without CSE for 8 weeks to establish a chronic murine asthma model. Airway hyperresponsiveness (AHR), airway inflammatory cells from bronchoalveolar lavage fluid, and the population of CD4+ T cells, ILCs, and macrophages in the lungs were studied to evaluate the effect of chronic CSE exposure on asthma. Results: Mice intranasally exposed to CSE along with OVA treatment (CSE/OVA) had significantly enhanced AHR, eosinophilic inflammation, increased IL- 13 and IL-17 producing CD4+ T cells compared to mice intranasally exposed to OVA only. On the contrary, the frequency of Foxp3+ in CD4+ T cells was reduced in the CSE/ OVA group. CSE enhanced the dendritic cell (DC) population, especially MHCII+ DC with antigen-presenting capacity. Among ILCs, the CSE/OVA group showed a significant increase of IL-13-producing type 2 ILCs, but not interferon-γ+ ILC1s and IL-17+ ILC3s. Among macrophages, alveolar macrophage and Ym-1 and FIZZ1 positive M2 macrophage populations were significantly induced by CSE exposure alone and when combined with OVA treatment. Conclusion: In this study, we showed that long-term exposure to cigarette smoke contributes to the inception and aggravation of asthmatic inflammation by enhancing DCs, ILC2, and M2 alveolar macrophage populations in the mouse model.

TNF-α and MMPs mediated mucus hypersecretion induced by cigarette smoke: An in vitro study

Cigarette smoke is one of the leading causes of oxidative stress due to high levels of free radicals, which in turn leads to the degradation of alveolar cell walls and development of emphysema. Cigarette smoking has been linked to chronic bronchitis, Chronic Obstructive Pulmonary Disease (COPD) and lung cancer as well. The aim of the present study was to observe the effect of cigarette smoke extract (CSE) on TNF-α and MMPs mediated mucus hypersecretion in A549 cell line. The MTT experiments showed that CSE caused a dose-dependent decline in the level of viability of A549 cells. In addition, AO/PI and Mitotracker Red staining assays demonstrated that CSE caused the A549 cells to undergo apoptosis. This was determined by observing the reduction in mitochondrial membrane potential. CSE was found to be responsible for the formation of intracellular ROS, which was observed by DCFDA staining through fluorescence microscopy. Approximately 65% migration rate was decreased in 20% CSE exposed cells. CSE exposure led to the significantly increased mRNA levels of TNF-α, MMP-7, and MMP-12, in comparison to the control cells. Additionally, the expression of MUC5AC and MUC5B was provoked by CSE as well. Human epithelial cells are stimulated by TNF-α and MMPs secreted mucus, as shown by expression of MUC5AC and MUC5B. CSE could induce mucus in lungs through TNF-α and MMPs mediated pathways.

Cigarette smoke extract impairs gingival epithelial barrier function

We previously showed that junctional adhesion molecule 1 (JAM1) and coxsackievirus and adenovirus receptor (CXADR), tight junction-associated proteins, have important roles to maintain epithelial barrier function in gingival tissues. Smoking is considered to be a significant risk factor for periodontal disease. The present study was conducted to examine the effects of cigarette smoke extract (CSE) on JAM1 and CXADR in human gingival epithelial cells. CSE was found to cause translocation of JAM1 from the cellular surface to EGFR-positive endosomes, whereas CXADR did not. Using a three-dimensional multilayered gingival epithelial tissue model, CSE administration was found to increase permeability to lipopolysaccharide and peptidoglycan, whereas overexpression of JAM1 in the tissue model prevented penetration by those substrates. Furthermore, vitamin C increased JAM1 expression, and inhibited penetration of LPS and PGN induced by CSE. These findings strongly suggest that CSE disrupts gingival barrier function via dislocation of JAM1, thus allowing bacterial virulence factors to penetrate into subepithelial tissues. Furthermore, they indicate that vitamin C increases JAM1 expression and prevents disruption of gingival barrier function by CSE.

Cigarette Smoke Extract and Lipopolysaccharide Induce Pyroptosis in Pulmonary Microvascular Endothelial Cells of Rats.

We studied the effect of cigarette smoke extract (CSE), LPS, or their combination on the activity and pyroptosis of pulmonary microvascular endothelial cells (PMVEC) in rats. PMVEC were cultured without treatment, with CSE in different concentrations (1-25%), with 20 ng/ml LPS, or with 20% CSE+20 ng/ml LPS. Cell viability was determined using the CCK8 kit, apoptosis was evaluated by flow cytometry, and cell morphology was evaluated using light microscopy. The content of IL-1β and IL-18 was measured by ELISA. CSE decreased cell viability in a dose-dependent manner. The morphology of cells in the CSE+LPS group showed the most significant cytomorphological changes and the highest pyroptosis rate. Flow cytometry showed that the apoptosis rates in the CSE and LPS groups were higher than in the control group, but the highest rate of apoptosis was revealed in the CSE+LPS group (p<0.01). The levels of IL-18 and IL-1β in the cell supernatant of the CSE, LPS, and CSE+LPS groups were significantly (p<0.01) increased in comparison with the control. These levels in the CSE+LPS group were higher (p<0.01) than in other groups. There were no differences between the CSE and LPS groups. Thus, the effect of CSE on cell viability is dose-dependent. Combined treatment with CSE+LPS can induce cell pyroptosis and increase the levels of inflammatory cytokines in PMVEC. These observations demonstrated that pyroptosis caused by CSE and LPS can play an important role in pulmonary vascular remodeling.

Modeling the effects of cigarette smoke extract on influenza B virus infections in mice.

Influenza B virus (IBV) is a major respiratory viral pathogen. Due to a lack of pandemic potential for IBV, there is a lag in research on IBV pathology and immunological responses compared to IAV. Therefore, the impact of various lifestyle and environmental factors on IBV infections, such as cigarette smoking (CS), remains elusive. Despite the increased risk and severity of IAV infections with CS, limited information exists on the impact of CS on IBV infections due to the absence of suitable animal models. To this end, we developed an animal model system by pre-treating mice for two weeks with cigarette smoke extract (CSE), then infected them with IBV and monitored the resulting pathological, immunological, and virological effects. Our results reveal that the CSE treatment decreased IBV specific IgG levels yet did not change viral replication in the upper airway/the lung, and weight recovery post infection. However, higher concentrations of CSE did result in higher mortality post infection. Together, this suggests that CS induced inflammation coupled with IBV infection resulted in exacerbated disease outcome.

Effects of cigarette smoke extracts (combustible and heated tobacco) on rat and human iPS cell-derived cardiomyocytes.

Smoking is a risk factor of cardiovascular diseases. However, direct effects on cardiomyocytes, especially on intracellular Ca2+ dynamics and on human cardiomyocytes, are not fully elucidated. In addition, the effects of heated cigarettes, which have been increasingly used in recent years, on human diseases have not been extensively studied. In this study, we compared the effects of cigarette smoke extracts (CSEs) from heated (Ploom X, IQOS) and combustible cigarettes (1R6F, Hi-Lite) on cell viability, contractile function and intracellular Ca2+ dynamics in rat and human iPS cell-derived cardiomyocytes. MTS assays indicated that all CSEs reduced cell viability of cultured myocytes, with toxicity in the order of combustible > heated CSEs. Functional analysis showed that 1% CSE significantly reduced the spontaneous beating rate of cultured cardiomyocytes only in the combustible cigarette group. In contrast, in freshly isolated cardiomyocytes, cell shortening was reduced in all CSE-treated groups. Intracellular Ca2+ measurement revealed that abnormal Ca2+ dynamics are induced by combustible CSEs. Kinetic analysis of Ca2+ transients suggests that CSE accelerates the rate of Ca2+ uptake into the sarcoplasmic reticulum (SR), but also causes excessive Ca2+ leakage from the SR, leading to diastolic Ca2+ overload. Similar contractile dysfunction (reduced spontaneous beating rate and contractility) was also observed in human iPS-derived cardiomyocytes. These results indicate that combustible cigarettes attenuate contractile function by altering intracellular Ca2+ dynamics. On the other hand, heated cigarettes were also found to exhibit myocardial toxic effects, albeit to a lesser degree than combustible cigarettes, suggesting the need for caution when smoking cigarettes.

PS-BPB09-3: CIGARETTE SMOKE EXTRACT INDUCES DNA DAMAGE AND TRIGGERS AN INNATE IMMUNE RESPONSE

Objective: Elevated blood pressure and tobacco smoking are causes of preventable mortality. The effects of tobacco smoking on blood pressure are complex and chronic effects are inconsistent. We have previously reported increased DNA damage in peripheral mononuclear cells of smokers compared to nonsmokers. In this study, we investigated the effects of cigarette smoke extract (CSE) on DNA damage and the physiological influence of DNA damage in endothelial cells. Design and method: The effect of CSE extracted from tobacco smoke was examined in human umbilical vein endothelial cells (HUVECs). CSE was added to HUVECs and the formation of DNA damage was quantified by fluorescent immunostaining. The mRNA expression of inflammatory cytokines was quantified by real-time RT PCR. Results: CSE increased double-strand breaks in HUVEC by 72 hours. CSE also increased oxidative DNA damage both in the nucleus and mitochondria, and decreased mitochondria membrane potential. Mitochondrial dysfunction partially induced mitochondrial outer membrane permeabilization, resulting in the partial activation of caspase-3 and nuclear translocation of caspase-activated deoxyribonuclease, which fragments DNA in the nucleus. It was suggested that this is one of the mechanisms of nuclear DNA double-strand breaks. CSE induced the accumulation of nuclear and mitochondrial DNA in the cytosol. We further examined whether accumulated cytosolic DNA activated cytosolic DNA-sensing pathways. The production of cGAMP, a second messenger in cGAS (a DNA-sensing receptor) signaling, was increased by CSE, followed by nuclear translocation of NF-kB and increased mRNA expression of IL-6. The increase in IL-6 expression was suppressed by si-cGAS. Conclusions: Our study revealed that continuous exposure to CSE induces DNA damages not only in the nucleus but also in the mitochondria, which leads to cytosolic DNA accumulation, and evokes chronic inflammation via the cGAS pathway.

Effects of cigarette smoke extract derived from heated tobacco products on the endoderm differentiation of human induced pluripotent stem cells.

Effects of cigarette smoke extract derived from heated tobacco products on the endoderm differentiation of human induced pluripotent stem cells.

Effects of cigarette smoke extract on mitochondrial function of macrophages

Objective: To investigate the effects of cigarette smoke extract (CSE) on the mitochondrial function of macrophages. Methods: RAW264.7 macrophages were used for the experiment in this study. When the cell density was about 70%, the old culture medium was abandoned, and the 100% CSE stock solution was diluted with serum-free DMEM and FBS into 1%, 5%, 15%, 25% and 90% CSE and added to the well plate. The cell activity of RAW264.7 cells treated with CSE at different concentrations for 24 h was detected by CCK-8 method. Then the optimal CSE concentration was selected to treat cells for 0 h, 24 h, 48 h or 72 h respectively, and CCK-8 assay was used to detect the cell activity of CSE treated cells at different time groups. After the cells were treated with 0%, 5% and 25% CSE for 24 hours, cell necrosis and apoptosis was detected by Annexin V-FITC /PI staining; Mitochondrial membrane damage of RAW 264.7 was detected by mitochondrial membrane potential assay kit with JC-1; Macrophages were stained with ROS-specific dye DCFH-DA, and then Flow cytometer was used to determine the fluorescence and the proportion of ROS-positive macrophages; the enhanced ATP assay kit was used to detect the intracellular ATP concentration. Results: ①Compared with 0% CSE, cell viability was increased significantly in 1% CSE group (P＜0.01), cell viability was decreased significantly when CSE concentration was above 5% (P＜0.05); Macrophages were treated with 5% CSE, and cell viability was decreased significantly with the increase of treatment time (P＜0.01). ②Compared with 0% CSE, 5% CSE and 25% CSE mainly caused macrophage necrosis, decreased mitochondrial membrane potential, increased ROS production and decreased ATP significantly (P＜0.05 or P＜0.01), and the changes were more significant in 25% CSE treatment group(P＜0.05 or P＜0.01). Conclusion: CSE may affect mitochondrial function of macrophages, leading to decreased cell viability and necrosis.

Cigarette smoke extract stimulates human pulmonary artery smooth muscle cell proliferation: Role of inflammation and oxidative stress.

Objective(s):Cigarette smoke may play a direct role in proliferation of human pulmonary artery smooth muscle cells (HPASMCs). However, the mechanism involved and the effect of interventions remain unclear. We aimed to evaluate the effect of cigarette smoke extract (CSE) on HPASMCs, explore the role of inflammation and oxidative stress, and the effects of Tempol and PDTC in this process.Materials and Methods:HPASMCs were subjected to normal control (NC), CSE, CSE+Tempol (CSE+T), and CSE+PDTC (CSE+P) groups. Proliferation of HPASMCs was measured by CCK-8 and Western blot. TNF-α, IL-6, MDA, and SOD levels were determined by ELISA and commercial kits. Nuclear translocation of NF-κB p65 was evaluated by western blot.Results:1%, 2.5%, and 5% CSE all promoted proliferation of HPASMCs, and effect of 1% CSE was the most significant, however, 7.5% and 10% CSE inhibited viability of cells (all P<0.05). Compared with the NC group, TNF-α, IL-6, and MDA levels increased, SOD activity decreased (all P<0.05), and NF-κB p65 expression in nuclei increased (P=0.04) in the CSE group. Tempol and PDTC inhibited the proliferation of HPASMCs induced by CSE (all P<0.05). And compared with the CSE group, TNF-α, IL-6, and MDA levels in CSE+T and CSE+P groups decreased, while SOD activity increased (all P<0.05). Tempol reduced the expression of NF-κB p65 in nuclei but did not achieve a significant difference (P=0.08). PDTC inhibited the nuclear translocation of NF-κB p65 (P=0.03).Conclusion:CSE stimulates HPASMCs proliferation in a certain concentration range. The CSE-induced proliferation of HPASMCs involved excessive inflammatory response and oxidative stress. Tempol and PDTC attenuate these effects of CSE on HPASMCs.

Effects of cigarette smoke extract derived from heated tobacco products on the proliferation of lung cancer stem cells

Epidemiological studies have suggested that cigarette smoking can increase a person’s risk of developing several types of cancer, including lung cancer. Lung cancer originates from cancer stem cells (CSCs), which constitute a minor cell population in tumors, and contribute to drug resistance and recurrence. Heated tobacco products (HTPs) produce aerosols that contain nicotine and toxic chemicals. Current evidence, however, is insufficient to accurately determine if HTPs are less harmful than burned cigarettes. This study has investigated the effects of cigarette smoke extract (CSE) from HTPs on lung CSCs in lung cancer cell lines. We found that CSEs induced the proliferation of lung CSCs and increased the expression levels of stem cell markers. In addition, CSE induced epithelial-mesenchymal transition (EMT) expression and cytokine production. These results suggest that HTPs can induce lung CSCs in vitro.

Cigarette smoke gas phase induces ferroptosis via PKC in tracheal epithelial cells

Cigarette smoking is one of the risk factors for respiratory diseases such as chronic obstructive pulmonary disease and emphysema. Cigarette smoke can be divided into two phases; tar (particle) phase including nicotine and gas phase. Although both phases of cigarette smoke have cytotoxic activity and affect respiratory system, the molecular mechanism for cytotoxicity has remained to be clarified. In this study, we have examined the effects of cigarette smoke extracts on tracheal epithelial cells and lung cells. Both tar and gas phases induced cell death. Ferrostatin-1 suppressed gas phase-induced cell death, whereas it had no effects on tar phase-induced cell death. Several unsaturated carbonyl compounds such as acrolein (ACR) and methyl vinyl ketone (MVK) are major cytotoxic compounds in the gas phase. Ferrostatin-1 also suppressed ACR- and MVK-induced cell death in tracheal epithelial cells. These results indicate that ACR and MVK in gas phase are critical factors for ferroptosis induction by cigarette smoke in the respiratory system. Since we have previously reported that ACR- and MVK-induced cell death is PKC-dependent in aorta smooth muscle cells, we have examined PKC inhibitors. The results suggest that novel and/or atypical PKCs involve in cigarette smoke-induced ferroptosis induction in tracheal epithelial cells.

A comparative study of the effects of cigarette smoke extracts (CSE) from combusted or heated cigarettes on contractile function, spontaneous beating rate, and intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; dynamics in rat ventricular myocytes.

A comparative study of the effects of cigarette smoke extracts (CSE) from combusted or heated cigarettes on contractile function, spontaneous beating rate, and intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; dynamics in rat ventricular myocytes.

Effects of cigarette smoke extract (CSE) on the contraction, spontaneous beating rate and intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; dynamics in adult and neonatal cardiomyocytes

Effects of cigarette smoke extract (CSE) on the contraction, spontaneous beating rate and intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; dynamics in adult and neonatal cardiomyocytes