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1.
Chem Biol Interact ; 333: 109321, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33186600

RESUMO

HPV infections in the oral cavity that progress to cancer are on the increase in the USA. Model systems to study co-factors for progression of these infections are lacking as HPVs are species-restricted and cannot grow in preclinical animal models. We have recently developed a mouse papillomavirus (MmuPV1) oral mucosal infection model that provides opportunities to test, for the first time, the hypothesis that tobacco carcinogens are co-factors that can impact the progression of oral papillomas to squamous cell carcinoma (SCC). Four cohorts of mice per sex were included: (1) infected with MmuPV1 and treated orally with DMSO-saline; (2) infected with MmuPV1 and treated orally with the tobacco carcinogen, dibenzo[def,p]chrysene (DBP); (3) uninfected and treated orally with DMSO-saline, and (4) uninfected and treated orally with DBP. Oral swabs were collected monthly for subsequent assessment of viral load. Oral tissues were collected for in situ viral DNA/RNA detection, viral protein staining, and pathological assessment for hyperplasia, papillomas and SCC at study termination. We observed increased rates of SCC in oral tissue infected with MmuPV1 and treated with DBP when compared to mice treated with DBP or virus individually, each of which showed minimal disease. Virally-infected epithelium showed strong levels of viral DNA/RNA and viral protein E4/L1 staining. In contrast, areas of SCC showed reduced viral DNA staining indicative of lower viral copy per nucleus but strong RNA signals. Several host markers (p120 ctn, p53, S100A9) were also examined in the mouse oral tissues; of particular significance, p120 ctn discriminated normal un-infected epithelium from SCC or papilloma epithelium. In summary, we have confirmed that our infection model is an excellent platform to assess the impact of co-factors including tobacco carcinogens for oral PV cancerous progression. Our findings can assist in the design of novel prevention/treatment strategies for HPV positive vs. HPV negative disease.


Assuntos
Crisenos/toxicidade , Progressão da Doença , Poluentes Ambientais/toxicidade , Neoplasias Bucais/patologia , Papillomaviridae/fisiologia , Fumaça/efeitos adversos , Tabaco/efeitos adversos , Animais , Carcinogênese/efeitos dos fármacos , Feminino , Genoma Viral/genética , Masculino , Camundongos , Neoplasias Bucais/virologia , Papillomaviridae/genética , Caracteres Sexuais , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
2.
Environ Pollut ; 268(Pt B): 115863, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33126161

RESUMO

Cigarette smoke (CS) affects immune functions, leading to severe outcomes in smokers. Robust evidence addresses the immunotoxic effects of combustible tobacco products. As heat-not-burn tobacco products (HNBT) vaporize lower levels of combustible products, we here compared the effects of cigarette smoke (CS) and HNBT vapor on Jurkat T cells. Cells were exposed to air, conventional cigarettes or heatsticks of HNBT for 30 min and were stimulated or not with phorbol myristate acetate (PMA). Cell viability, proliferation, reactive oxygen species (ROS) production, 8-OHdG, MAP-kinases and nuclear factor κB (NFκB) activation and metallothionein expression (MTs) were assessed by flow cytometry; nitric oxide (NO) and cytokine levels were measured by Griess reaction and ELISA, respectively. Levels of metals in the exposure chambers were quantified by inductively coupled plasma mass spectrometry. MT expressions were quantified by immunohistochemistry in the lungs and liver of C57Bl/6 mice exposed to CS, HNBT or air (1 h, twice a day for five days: via inhalation). While both CS and HBNT exposures increased cell death, CS led to a higher number of necrotic cells, increased the production of ROS, NO, inflammatory cytokines and MTs when compared to HNBT-exposed cells, and led to a higher expression of MTs in mice. CS released higher amounts of metals. CS and HNBT exposures decreased PMA-induced interleukin-2 (IL-2) secretion and impaired Jurkat proliferation, effects also seen in cells exposed to nicotine. Although HNBT vapor does not activate T cells as CS does, exposure to both HNBT and CS suppressed proliferation and IL-2 release, a pivotal cytokine involved with T cell proliferation and tolerance, and this effect may be related to nicotine content in both products.


Assuntos
Produtos do Tabaco , Tabaco , Animais , Temperatura Alta , Camundongos , Fumaça/efeitos adversos , Fumar
3.
PLoS One ; 15(11): e0242789, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33237957

RESUMO

There has been an increase in the usage of heat-not-burn (HNB) cigarette products. However, their effects on alveolar epithelial cells (AECs) remain unknown. AECs are the target cells of conventional cigarette smoking-related respiratory diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and lung cancer whose pathogenesis involves oxidative stress. In this study, primary rat AECs were isolated, cultured and stimulated by HNB cigarette smoke extract (CSE). Our data indicate that rat AECs exposed to HNB CSE induced oxidative stress response genes (e.g. Hmox-1, Gsta1, Gsta3 and Nqo1). We also compared the oxidative stress response between two different types of AECs, alveolar type I-like (ATI-like) cells and type II (ATII) cells, and between two different types of cigarette, HNB cigarettes and conventional cigarettes. The expressions of Gsta1, Gsta3 and Nqo1 were higher in ATII cells than ATI-like cells in response to HNB and conventional cigarettes, but there was no significant difference in their expression levels between HNB cigarette and conventional cigarette. Taken together, our results suggest that HNB cigarettes have the similar potential as conventional cigarette products to induce oxidative stress response in AECs.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Fumar Cigarros/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Alvéolos Pulmonares/efeitos dos fármacos , Células Epiteliais Alveolares/patologia , Animais , Modelos Animais de Doenças , Sistemas Eletrônicos de Liberação de Nicotina , Temperatura Alta/efeitos adversos , Humanos , Oxirredução/efeitos dos fármacos , Cultura Primária de Células , Alvéolos Pulmonares/patologia , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Ratos , Fumaça/efeitos adversos , Tabaco/efeitos adversos
4.
Life Sci ; 263: 118753, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33189821

RESUMO

AIMS: Smoking is an important risk factor for the development of chronic obstructive pulmonary disease and cardiovascular diseases. This study aimed to further elucidate the role of ceramides, as a key lipid class dysregulated in disease states. MAIN METHODS: In this article we developed and validated LC-MS/MS method for ceramides (Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1(15Z)) for the absolute quantification. We deployed it together with proteomics and transcriptomic analysis to assess the effects of cigarette smoke (CS) from the reference cigarette as well as aerosols from heat-not-burn (HnB) tobacco and e-vapor products in apolipoprotein E-deficient (ApoE-/-) mice over several time points. KEY FINDINGS: In the lungs, CS exposure substantially elevated the ratios of Cer(d18:1/24:0) and Cer(d18:1/24:1) to Cer(d18:1/18:0) in two independent ApoE-/- mouse inhalation studies. Data from previous studies, in both ApoE-/- and wild-type mice, further confirmed the reproducibility of this finding. Elevation of these ceramide ratios was also observed in plasma/serum, the liver, and-for the Cer(d18:1/24:1(15Z)) to Cer(d18:1/18:0) ratio-the abdominal aorta. Also, the levels of acid ceramidase (Asah1) and glucocerebrosidase (Gba)-lysosomal enzymes involved in the hydrolysis of glucosylceramides-were consistently elevated in the lungs after CS exposure. In contrast, exposure to HnB tobacco product and e-vapor aerosols did not induce significant changes in the ceramide profiles or associated enzymes. SIGNIFICANCE: Our work in mice contributes to the accumulating evidence on the importance of ceramide ratios as biologically relevant markers for respiratory disorders, adding to their already demonstrated role in cardiovascular disease risk assessment in humans.


Assuntos
Apolipoproteínas E/genética , Ceramidas/metabolismo , Vapor do Cigarro Eletrônico/efeitos adversos , Pulmão/metabolismo , Fumaça/efeitos adversos , Aerossóis/efeitos adversos , Animais , Ceramidas/análise , Cromatografia Líquida/métodos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteômica , Fatores de Risco , Espectrometria de Massas em Tandem/métodos , Fatores de Tempo
5.
J Vis Exp ; (164)2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33165327

RESUMO

Close to 14% of adults in the United States were reported to smoke cigarettes in 2018. The effects of cigarette smoke (CS) on lungs and cardiovascular diseases have been widely studied, however, the impact of CS in other tissues and organs such as blood and bone marrow remain incompletely defined. Finding the appropriate system to study the effects of CS in rodents can be prohibitively expensive and require the purchase of commercially available systems. Thus, we set out to build an affordable, reliable, and versatile system to study the pathologic effects of CS in mice. This whole-body inhalation exposure system (WBIS) set-up mimics the breathing and puffing of cigarettes by alternating exposure to CS and clean air. Here we show that this do-it-yourself (DIY) system induces airway inflammation and lung emphysema in mice after 4-months of cigarette smoke exposure. The effects of whole-body inhalation (WBI) of CS on hematopoietic stem and progenitor cells (HSPCs) in the bone marrow using this apparatus are also shown.


Assuntos
Modelos Animais de Doenças , Exposição por Inalação/efeitos adversos , Fumaça/efeitos adversos , Produtos do Tabaco/efeitos adversos , Animais , Exposição por Inalação/análise , Camundongos , Enfisema Pulmonar/induzido quimicamente
6.
Toxicol Lett ; 335: 51-63, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33091563

RESUMO

Electronic cigarettes (e-cigarettes) and tobacco heating products (THPs) have reduced yields of toxicants and have recently emerged as a potentially safer alternative to combustible cigarettes. To understand if reduced toxicant exposure is associated with reductions in biological responses, there is a need for high-quality pre-clinical in vitro studies. Here, we investigated the cytotoxic response of human umbilical vein endothelial cells to conventional cigarette aqueous aerosol extracts (AqE) and highly concentrated AqEs from e-cigarettes (two generations of atomisers) and THPs (two variants). All AqE samples were generated by a standardized methodology and characterized for nicotine, propylene glycol and vegetable glycerol. The cigarette AqE caused a maximum 100 ± 0.00 % reduction in cell viability at 35 % dose (2.80 puffs) as opposed to 96.63 ± 2.73 % at 50 % (20 puffs) and 99.85 ± 0.23 % at 75 % (30 puffs) for the two THP variants (glo Bright Tobacco, glo Rich Tobacco), and 99.07 ± 1.61 % at the neat ePen2.0 e-cigarette (200 puffs). The AqE of the remaining e-cigarettes either resulted in an incomplete dose-response or did not elicit any response. The methods utilized were suitably sensitive to not only differentiate between cigarette, THP and e-cigarette aerosols but also to distinguish between products within each product category.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Substâncias Perigosas/toxicidade , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Fumaça/efeitos adversos , Produtos do Tabaco/toxicidade , Aerossóis , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Calefação , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos
7.
Mol Pharmacol ; 98(6): 658-668, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33055223

RESUMO

CYP2A enzymes metabolically inactivate nicotine and activate tobacco-derived procarcinogens [e.g., 4-[methylnitrosamino]-1-(3-pyridyl)-1-butanone]. Smoking decreases nicotine clearance, and chronic nicotine reduces hepatic CYP2A activity. However, little is known about the impact of smoking or nicotine on the expression of CYP2A in the lung. We investigated 1) the levels of human lung CYP2A mRNA in smokers versus nonsmokers and 2) the impact of daily nicotine treatment on lung CYP2A protein levels in African green monkeys (AGMs). Lung CYP2A13, CYP2A6, and CYP2A7 (and CYP1A2) mRNA levels in smokers and nonsmokers were assessed in Gene Expression Omnibus data sets (GSE30063, GSE108134, and GSE11784). The impact of chronic, twice-daily, subcutaneous nicotine at two doses (0.3 and 0.5 mg/kg) versus vehicle on lung CYP2A protein levels was assessed. The impact of ethanol self-administration was also investigated, with and without nicotine treatment. Smokers versus nonsmokers (from GSE30063 and GSE108134) had lower (1.04- to 1.12-fold) levels of lung CYP2A13, CYP2A6, and CYP2A7 (and higher CYP1A2) mRNA. Both doses of nicotine tested decreased AGM lung CYP2A protein (3- to 7-fold). Ethanol self-administration had no effect on AGM lung CYP2A protein, and there was no interaction between ethanol and nicotine. Our results suggest that smoking was associated with a reduction in human lung CYP2A13, CYP2A6, and CYP2A7 mRNA, consistent with the role of nicotine treatment in reducing AGM lung CYP2A protein. This regulation by smoking/nicotine will increase interindividual variation in lung CYP2A levels, which may impact the localized metabolism of inhaled drugs and tobacco smoke procarcinogens. SIGNIFICANCE STATEMENT: CYP2A13 and CYP2A6 are expressed in the lung and may contribute to local procarcinogen activation. Smokers had lower lung CYP2A mRNA levels compared with nonsmokers. Lung CYP2A protein expression was decreased by systemic treatment with nicotine. Decreased lung CYP2A expression may alter smoking-related lung cancer risk and tissue damage from other inhaled toxins. This novel regulatory impact of nicotine, including nicotine found in smoking-cessation nicotine-replacement therapies, may have potential benefits on smoking-related lung cancer risk.


Assuntos
Hidrocarboneto de Aril Hidroxilases/metabolismo , Pulmão/patologia , Fumar/patologia , Esteroide Hidroxilases/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Hidrocarboneto de Aril Hidroxilases/análise , Hidrocarboneto de Aril Hidroxilases/genética , Chlorocebus aethiops , Conjuntos de Dados como Assunto , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Pulmão/efeitos dos fármacos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/prevenção & controle , Masculino , Microssomos Hepáticos , Nicotina/toxicidade , não Fumantes , RNA Mensageiro/análise , Análise de Sequência de RNA , Fumaça/efeitos adversos , Fumantes , Fumar/efeitos adversos , Esteroide Hidroxilases/análise , Esteroide Hidroxilases/genética , Tabaco/química , Tabaco/toxicidade
9.
Mol Pharmacol ; 98(5): 586-597, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32938721

RESUMO

This study investigated the roles of transient receptor potential (TRP) ankyrin-1 (TRPA1) and TRP vanilloid-3 (TRPV3) in regulating endoplasmic reticulum stress (ERS) and cytotoxicity in human bronchial epithelial cells (HBECs) treated with pneumotoxic wood smoke particulate matter (WSPM) and chemical agonists of each channel. Functions of TRPA1 and TRPV3 in pulmonary epithelial cells remain largely undefined. This study shows that TRPA1 activity localizes to the plasma membrane and endoplasmic reticulum (ER) of cells, whereas TRPV3 resides primarily in the ER. Additionally, treatment of cells using moderately cytotoxic concentrations of pine WSPM, carvacrol, and other TRPA1 agonists caused ERS as a function of both TRPA1 and TRPV3 activities. Specifically, ERS and cytotoxicity were attenuated by TRPA1 inhibition, whereas inhibiting TRPV3 exacerbated ERS and cytotoxicity. Interestingly, after treatment with pine WSPM, TRPA1 transcription was suppressed, whereas TRPV3 was increased. TRPV3 overexpression in HBECs conferred resistance to ERS and an attenuation of ERS-associated cell cycle arrest caused by WSPM and multiple prototypical ERS-inducing agents. Alternatively, short hairpin RNA-mediated knockdown of TRPV3, like the TRPV3 antagonist, exacerbated ERS. This study reveals previously undocumented roles for TRPA1 in promoting pathologic ERS and cytotoxicity elicited by pneumotoxic WSPM and TRPA1 agonists, and a unique role for TRPV3 in fettering pathologic facets of the integrated ERS response. SIGNIFICANCE STATEMENT: These findings provide new insights into how wood smoke particulate matter and other transient receptor potential ankyrin-1 (TRPA1) and transient receptor potential vanilloid-3 (TRPV3) agonists can affect human bronchial epithelial cells and highlight novel physiological and pathophysiological roles for TRPA1 and TRPV3 in these cells.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Material Particulado/administração & dosagem , Fumaça/efeitos adversos , Canal de Cátion TRPA1/metabolismo , Canais de Cátion TRPV/metabolismo , Linhagem Celular , Cimenos/efeitos adversos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Células Epiteliais/metabolismo , Células HEK293 , Humanos , Pulmão/metabolismo , Pinus/efeitos adversos , Canais de Receptores Transientes de Potencial/metabolismo , Madeira/efeitos adversos
10.
Am J Physiol Lung Cell Mol Physiol ; 319(6): L1021-L1035, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32964723

RESUMO

S100 calcium-binding protein A9 (S100A9) is elevated in plasma and bronchoalveolar lavage fluid (BALF) of patients with chronic obstructive pulmonary disease (COPD), and aging enhances S100A9 expression in several tissues. Currently, the direct impact of S100A9-mediated signaling on lung function and within the aging lung is unknown. Here, we observed that elevated S100A9 levels in human BALF correlated with age. Elevated lung levels of S100A9 were higher in older mice compared with in young animals and coincided with pulmonary function changes. Both acute and chronic exposure to cigarette smoke enhanced S100A9 levels in age-matched mice. To examine the direct role of S100A9 on the development of COPD, S100a9-/- mice or mice administered paquinimod were exposed to chronic cigarette smoke. S100A9 depletion and inhibition attenuated the loss of lung function, pressure-volume loops, airway inflammation, lung compliance, and forced expiratory volume in 0.05 s/forced vital capacity, compared with age-matched wild-type or vehicle-administered animals. Loss of S100a9 signaling reduced cigarette smoke-induced airspace enlargement, alveolar remodeling, lung destruction, ERK and c-RAF phosphorylation, matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and keratinocyte-derived chemokine (KC) release into the airways. Paquinimod administered to nonsmoked, aged animals reduced age-associated loss of lung function. Since fibroblasts play a major role in the production and maintenance of extracellular matrix in emphysema, primary lung fibroblasts were treated with the ERK inhibitor LY3214996 or the c-RAF inhibitor GW5074, resulting in less S100A9-induced MMP-3, MMP-9, MCP-1, IL-6, and IL-8. Silencing Toll-like receptor 4 (TLR4), receptor for advanced glycation endproducts (RAGE), or extracellular matrix metalloproteinase inducer (EMMPRIN) prevented S100A9-induced phosphorylation of ERK and c-RAF. Our data suggest that S100A9 signaling contributes to the progression of smoke-induced and age-related COPD.


Assuntos
Calgranulina B/metabolismo , Mediadores da Inflamação/metabolismo , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumaça/efeitos adversos , Animais , Pulmão/metabolismo , Camundongos , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/metabolismo , Enfisema Pulmonar/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Capacidade Vital/fisiologia
11.
F1000Res ; 9: 769, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32953091

RESUMO

Background: Numerous successful therapies developed for human medicine involve animal experimentation. Animal studies that are focused solely on translational potential, may not sufficiently document unexpected outcomes. Considerable amounts of data from such studies could be used to advance veterinary science. For example, sheep are increasingly being used as models of intensive care and therefore, data arising from such models must be published. In this study, the hypothesis is that there is little information describing cardiorespiratory physiological data from sheep models of intensive care and the author aimed to analyse such data to provide biological information that is currently not available for sheep that received extracorporeal life support (ECLS) following acute smoke-induced lung injury. Methods: Nineteen mechanically ventilated adult ewes undergoing intensive care during evaluation of a form of ECLS (treatment) for acute lung injury were used to collate clinical observations. Eight sheep were injured by acute smoke inhalation prior to treatment (injured/treated), while another eight were not injured but treated (uninjured/treated). Two sheep were injured but not treated (injured/untreated), while one received room air instead of smoke as the injury and was not treated (placebo/untreated). The data were then analysed for 11 physiological categories and compared between the two treated groups. Results: Compared with the baseline, treatment contributed to and exacerbated the deterioration of pulmonary pathology by reducing lung compliance and the arterial oxygen partial pressure to fractional inspired oxygen (PaO 2/FiO 2) ratio. The oxygen extraction index changes mirrored those of the PaO 2/FiO 2 ratio. Decreasing coronary perfusion pressure predicted the severity of cardiopulmonary injury. Conclusions: These novel observations could help in understanding similar pathology such as that which occurs in animal victims of smoke inhalation from house or bush fires, aspiration pneumonia secondary to tick paralysis and in the management of the severe coronavirus disease 2019 (COVID-19) in humans.


Assuntos
Lesão Pulmonar Aguda/fisiopatologia , Lesão Pulmonar Aguda/terapia , Oxigenação por Membrana Extracorpórea , Fumaça/efeitos adversos , Animais , Circulação Coronária , Feminino , Oxigênio/sangue , Pressão Parcial , Ovinos
12.
Mutat Res ; 856-857: 503230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32928375

RESUMO

This work investigates a completely novel and experimental concept of exposing L5178Y cells at the air-agar-interface to mainstream cigarette smoke aerosol (Kentucky reference 3R4F). This study highlights the associated challenges of combining a suspension cell line alongside an in vitro aerosol exposure system. To achieve a monolayer, cells were 'seeded' in a concentrated cell super-mix suspension onto an RPMI/agar-matrix -base. The resulting cell suspension media was adsorbed into the agar base leaving the L5178Y cells lightly suspended on the agar surface, approximating a monolayer. Cells were deemed supportable on the agar-matrix, viable and recoverable. Using Vitrocell VC 10 exposure system and the Ames 4 exposure module, L5178Y cells were successfully exposed to a dynamic cigarette smoke aerosol, recovered and assessed for mutant frequencies, using standard assay procedures. Method development included assessment of flowing air conditions, plating efficiency and recovery of L5178Y cells from the agar-matrix surface. Positive controls MMS and B[a]P were successfully incorporated into the agar-matrix and metabolic activation was achieved by S-9 incorporation into the same agar-base-matrix. B[a]P demonstrated metabolic activation and positive response, suggesting a clear cellular interaction with the agar-matrix. Whole smoke exposed cells in the presence of metabolic activation showed a clear dose response and increasing mutant frequencies, well in excess of the controls (air and incubator) and the global evaluation factor following a 2 or 3 day expression period. This experimental concept demonstrates that L5178Y cells can be exposed to cigarette smoke aerosol, using a completely novel and a previously untested approach. Although this work successfully demonstrates the approach is viable and cells can be plated and maintained on an agar-matrix, more optimisation and robustness assessment is required before it can be considered fully adapted and used alongside other whole aerosol methodologies for the assessment of cigarette smoke and other inhaled aerosols.


Assuntos
Linfoma/patologia , Testes de Mutagenicidade , Mutagênicos/toxicidade , Fumaça/efeitos adversos , Aerossóis/farmacologia , Aerossóis/toxicidade , Ágar/química , Ar , Animais , Linhagem Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Linfoma/induzido quimicamente , Camundongos , Mutagênicos/farmacologia
15.
N C Med J ; 81(5): 320-323, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32900895

RESUMO

Preventing the adverse health impacts of wildfire smoke involves helping people understand if they are at risk, and the actions they can take to limit exposure. Cooperation between land managers, public health officials, and the health care system could alert the public to take actions that reduce wildfire smoke-related health risks.


Assuntos
Exposição Ambiental/efeitos adversos , Relações Interinstitucionais , Fumaça/efeitos adversos , Incêndios Florestais , Conservação dos Recursos Naturais , Assistência à Saúde , Humanos , Saúde Pública , Risco
16.
Am J Physiol Lung Cell Mol Physiol ; 319(4): L717-L727, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32845704

RESUMO

Most of electronic cigarette (e-cigarette) users are also smoking tobacco cigarettes. Because of the relative novelty of this habit, very little is known on the impact of vaping on pulmonary health, even less on the potential interactions of dual e-cigarette and tobacco cigarette use. Therefore, we used well-established mouse models to investigate the impact of dual exposure to e-cigarette vapors and tobacco cigarette smoke on lung homeostasis. Groups of female BALB/c mice were exposed to room air, tobacco smoke only, nicotine-free flavor-free e-cigarette vapors only or both tobacco smoke and e-cigarette vapors. Moreover, since tobacco smoke and electronic cigarette vapors both affect circadian processes in the lungs, groups of mice were euthanized at two different time points during the day. We found that dual-exposed mice had altered lung circadian gene expression compared with mice exposed to tobacco smoke alone. Dual-exposed mice also had different frequencies of dendritic cells, macrophages, and neutrophils in the lung tissue compared with mice exposed to tobacco smoke alone, an observation also valid for B-lymphocytes and CD4+ and CD8+ T lymphocytes. Exposure to e-cigarette vapors also impacted the levels of immunoglobulins in the bronchoalveolar lavage and serum. Finally, e-cigarette and dual exposures increased airway resistance compared with mice exposed to room air or tobacco smoke alone, respectively. Taken together, these data suggest that e-cigarette vapors, even without nicotine or flavors, could affect how the lungs react to tobacco cigarette smoke exposure in dual users, potentially altering the pathological course triggered by smoking.


Assuntos
Linfócitos B/efeitos dos fármacos , Vapor do Cigarro Eletrônico/efeitos adversos , Fumaça/efeitos adversos , Fumar/efeitos adversos , Animais , Sistemas Eletrônicos de Liberação de Nicotina , Pulmão/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Nicotina/metabolismo , Nicotina/farmacologia
17.
Sci Rep ; 10(1): 12796, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732964

RESUMO

Cigarette smoke exposure (CS) is the main risk factor for chronic obstructive pulmonary disease (COPD). Macrophages have an important role in COPD because they release pro-inflammatory and anti-inflammatory cytokines. The present study's we investigate the functional changes in macrophages and monocytes exposed to cigarette smoke extract (CSE). Herein, using human monocyte-derived macrophages (MDMs) from healthy donors and we found that CSE was not associated with significant changes in the production of pro inflammatory cytokines by MDMs. In contrast, exposure to CSE suppressed the production of IL-6 and Gro-a/CXCL1 by LPS-stimulated-MDMs, but had an additive effect on the release of IL-8/CXCL8 and MCP1/CCL2. However, CSE exposure was associated with greater production, TARC/CCL-17 and CCL22/MDC. Moreover, MDMs displayed a lower uptake capacity after CSE exposure. We identify, for what is to our knowledge the first time that monocytes from patients with COPD produced less IL-8/CXCL8 and Gro-α/CXCL1 after LPS stimulation and produced higher levels of TARC/CCL17 and MDC/CCL-22 after IL-4 stimulation. Our present results highlighted a skewed immune response, with an imbalance in M1 vs. M2 cytokine production. In conclusion, exposure to CS has contrasting, multifaceted effects on macrophages and monocytes. Our data may provide a better understanding of the mechanisms underlying COPD.


Assuntos
Fumar Cigarros/efeitos adversos , Macrófagos/imunologia , Monócitos/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Fumaça/efeitos adversos , Tabaco/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Citocinas/metabolismo , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Fatores de Risco
18.
Environ Sci Technol ; 54(19): 11838-11847, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32857515

RESUMO

Wildfires have a significant adverse impact on air quality in the United States (US). To understand the potential health impacts of wildfire smoke, many epidemiology studies rely on concentrations of fine particulate matter (PM) as a smoke tracer. However, there are many gas-phase hazardous air pollutants (HAPs) identified by the Environmental Protection Agency (EPA) that are also present in wildfire smoke plumes. Using observations from the Western Wildfire Experiment for Cloud Chemistry, Aerosol Absorption, and Nitrogen (WE-CAN), a 2018 aircraft-based field campaign that measured HAPs and PM in western US wildfire smoke plumes, we identify the relationships between HAPs and associated health risks, PM, and smoke age. We find the ratios between acute, chronic noncancer, and chronic cancer HAPs health risk and PM in smoke decrease as a function of smoke age by up to 72% from fresh (<1 day of aging) to old (>3 days of aging) smoke. We show that acrolein, formaldehyde, benzene, and hydrogen cyanide are the dominant contributors to gas-phase HAPs risk in smoke plumes. Finally, we use ratios of HAPs to PM along with annual average smoke-specific PM to estimate current and potential future smoke HAPs risks.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Incêndios Florestais , Poluentes Atmosféricos/análise , Material Particulado/análise , Fumaça/efeitos adversos , Fumaça/análise , Estados Unidos
20.
Biochim Biophys Acta Gen Subj ; 1864(11): 129699, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32738274

RESUMO

BACKGROUND: Surfactant proteins (SP) A and D belong to collectin family proteins, which play important roles in innate immune response in the lung. We previously demonstrated that cigarette smoke (CS) increases the acrolein modification of SP-A, thereby impairing the innate immune abilities of this protein. In this study, we focused on the effects of CS and its component, acrolein, on the innate immunity role of another collectin, SP-D. METHODS: To determine whether aldehyde directly affects SP-D, we examined the lungs of mice exposed to CS for 1 week and detected aldehyde-modified SP-D using an aldehyde reactive probe. The structural changes in CS extract (CSE) or acrolein-exposed recombinant human (h)SP-D were determined by western blot, liquid chromatography-electrospray ionization tandem mass spectrometry, and blue native-polyacrylamide gel electrophoresis analyses. Innate immune functions of SP-D were determined by bacteria growth and macrophage phagocytosis. RESULTS: Aldehyde-modified SP-D as well as SP-A was detected in the lungs of mice exposed to CS for 1 week. Exposure of hSP-D to CSE or acrolein induced an increased higher-molecular -weight of hSP-D and acrolein induced modification of five lysine residues in hSP-D. These modifications led to disruption of the multimer structure of SP-D and attenuated its ability to inhibit bacterial growth and activate macrophage phagocytosis. CONCLUSION: CS induced acrolein modification in SP-D, which in turn induced structural and functional defects in SP-D. GENERAL SIGNIFICANCE: These results suggest that CS-induced structural and functional defects in SP-D contribute to the dysfunction of innate immune responses in the lung following CS exposure.


Assuntos
Acroleína/efeitos adversos , Imunidade Inata , Pulmão/imunologia , Proteína D Associada a Surfactante Pulmonar/imunologia , Fumaça/efeitos adversos , Fumar Tabaco/efeitos adversos , Acroleína/análise , Animais , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose/efeitos dos fármacos , Proteína D Associada a Surfactante Pulmonar/análise , Proteínas Recombinantes/análise , Proteínas Recombinantes/imunologia , Fumaça/análise , Tabaco/química , Fumar Tabaco/imunologia
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