RESUMEN
Several epidemiological studies have demonstrated that particulate matter (PM) in air pollution can be involved in the genesis or aggravation of different cardiovascular, respiratory, perinatal, and cancer diseases. This study assessed the in vitro effects of PM10 on the secretion of cytokines by a human monocytic cell line (THP-1). We compared the chemotactic, pro-inflammatory, and anti-inflammatory cytokines induced by PM10 collected for two years during three different seasons in five different Mexico City locations. MIP-1α, IP-10, MCP-1, TNF-α, and VEGF were the main secretion products after stimulation with 80 µg/mL of PM10 for 24 h. The THP-1 cells showed a differential response to PM10 obtained in the different sites of Mexico City. The PM10 from the north and the central city areas induced a higher pro-inflammatory cytokine response than those from the south. Seasonal pro-inflammatory cytokine secretion always exceeded anti-inflammatory secretion. The rainy-season-derived particles caused the lowest pro-inflammatory effects. We concluded that toxicological assessment of airborne particles provides evidence supporting their potential role in the chronic exacerbation of local or systemic inflammatory responses that may worsen the evolution of some chronic diseases.
RESUMEN
Exposure to fine particulate matter (PM2.5) induces airway inflammation and hyperreactivity that lead to asthma. The mechanisms involved are still under investigation. We investigated the effect of resveratrol (3,4',5-trihydroxystilbene) (RES) on airway hyperresponsiveness, inflammation and CYP1A1 protein expression (an aryl hydrocarbon receptor (AhR) target) induced by PM2.5 exposure in an allergic asthma experimental guinea pig model. The polyphenolic compound RES was used due to its antioxidant and anti-inflammatory properties and as an antagonist of the AhR; thus, providing mechanistic insights. Animals were sensitized with aluminum hydroxide and ovalbumin and exposed to filtered air or PM2.5. Exposure to PM2.5 was conducted using a whole-body chamber particle concentrator (5 h/day) for 15 days. Animals received saline solution or RES (10 mg/kg per day) orally for 21 days simultaneously to the OVA challenge or PM2.5 exposure. PM2.5 exposure (mean 433 ± 111 µg/m3 in the exposure chamber) in OVA challenged animals induced an asthma-like phenotype characterized by increased baseline lung resistance (Rrs) and central airway resistance (Rn) in response to acetylcholine (ACh) evaluated using a flexiVent system®. A parallel increase of pro-inflammatory cytokines (IL-6, IL-17, TNF-α and IFN-γ), inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid (BALF) and lung CYP1A1 increase also occurred. RES significantly inhibited airway hyperresponsiveness, inflammation, and CYP1A1 protein expression in the OVA-challenged PM2.5 exposed animals. In summary, with the use of RES we demonstrate that PM-induced airway hyperreactivity is modulated by the inflammatory response via the AhR pathway in an allergic asthma guinea pig model.
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Asma/inducido químicamente , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/agonistas , Pulmón/efectos de los fármacos , Material Particulado/toxicidad , Neumonía/inducido químicamente , Receptores de Hidrocarburo de Aril/agonistas , Hidróxido de Aluminio , Animales , Antiasmáticos/farmacología , Antiinflamatorios/farmacología , Asma/inmunología , Asma/metabolismo , Asma/prevención & control , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Cobayas , Mediadores de Inflamación/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Ovalbúmina , Tamaño de la Partícula , Neumonía/inmunología , Neumonía/metabolismo , Neumonía/prevención & control , Receptores de Hidrocarburo de Aril/metabolismo , Resveratrol/farmacología , Transducción de SeñalRESUMEN
Epidemiological studies have associated long-term exposure to environmental air pollution particulate matter (PM) with the development of diverse health problems. They include infectious respiratory diseases related to the deregulation of some innate immune response mechanisms, such as the host defense peptides' expression. Herein, we evaluated in BALB/c mice the effect of long-standing exposure (60 days) to urban-PM from the south of Mexico City, with aerodynamic diameters below 2.5 µm (PM2.5) and 10 µm (PM10) on the lung's gene expression and production of three host defense peptides (HDPs); murine beta-defensin-3, -4 (mBD-3, mBD-4) and cathelin-related antimicrobial peptide (CRAMP). We also evaluated mRNA levels of Il1b and Il10, two cytokines related to the expression of host defense peptides. Exposure to PM2.5 and PM10 differentially induced lung inflammation, being PM2.5, which caused higher inflammation levels, probably associated with a differential deposition on the airways, that facilitate the interaction with alveolar macrophages. Inflammation levels were associated with an early upregulation of the three HDPs assessed and an increment in Il1b mRNA levels. Interestingly, after 28 days of exposure, Il10 mRNA upregulation was observed and was associated with the downregulation of HDPs and Il1b mRNA levels. The upregulation of Il10 mRNA and suppression of HDPs might facilitate microbial colonization and the development of diseases associated with long-term exposure to PM.
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Contaminantes Atmosféricos/toxicidad , Catelicidinas/metabolismo , Interleucina-1beta/metabolismo , Material Particulado/toxicidad , Neumonía/patología , beta-Defensinas/metabolismo , Animales , Catelicidinas/genética , Interleucina-1beta/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Neumonía/etiología , Neumonía/metabolismo , beta-Defensinas/genéticaRESUMEN
Acute leukemia is the most common childhood cancer and has been associated with exposure to environmental carcinogens. This study aimed to identify clusters of acute childhood leukemia (ACL) cases and analyze their relationship with proximity to industrial sources of air pollution in three capital cities in Colombia during 2000-2015. Incident ACL cases were obtained from the population cancer registries for the cities of Bucaramanga, Cali, and Medellín. The inventory of industrial sources of emissions to the air was obtained from the regional environmental authorities and industrial conglomerates were identified. The Kulldorf's circular scan test was used to detect city clusters and to identify clusters around industrial conglomerates. Multivariable spatial modeling assessed the effect of distance and direction from the industrial conglomerates controlling for socioeconomic status. We identified industrials sectors within a buffer of 1 km around industrial conglomerates related to the ACL clusters. Incidence rates showed geographical heterogeneity with low spatial autocorrelation within cities. The spatio-temporal tests identified one cluster in each city. The industries located within 1 km around the ACL clusters identified in the three cities represent different sectors. Exposure to air pollution from industrial sources might be contributing to the incidence of ACL cases in urban settings in Colombia.
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Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Monitoreo del Ambiente , Leucemia/inducido químicamente , Características de la Residencia/estadística & datos numéricos , Contaminación del Aire/análisis , Niño , Ciudades , Colombia/epidemiología , Femenino , Humanos , Leucemia/epidemiología , Masculino , Material Particulado/análisis , Análisis de Área PequeñaRESUMEN
Air pollution in developing countries is a growing concern. It is associated with urbanization and social and economic structures. The understanding of how social factors can influence the perception and the potential impact of air pollution have not been addressed sufficiently. This paper addresses the social vulnerability and exposure to PM10 association and its influence on the air quality perception of residents in Mexicali, a Mexico-US border city. This study used individual variables and population census data, as well as statistical and spatial analyses. A cluster of socially vulnerable populations with high exposure to coarse particulate matter (PM10) was found in the city's peripheral areas. The spatial distribution of the local perception of air quality varied by the exposure zones of the estimated PM10 concentrations. Respondents living in very high exposure areas perceive air quality as "poor," contrarily to a worse perception in areas of intermediate and lower exposure to PM10. Proximity to stationary sources of pollution was associated with a poor perception of air quality. Results also indicate that low household income and poor air quality perceived at the place of residence negatively influences the perceived changes in the air quality over time. The knowledge of chronic health effects related to air pollution was scarce in the sampled population, especially in the areas with very high exposure and high social vulnerability. These findings can serve as a support in local air quality management.
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Contaminantes Atmosféricos , Contaminación del Aire , Clase Social , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Ciudades , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente , Humanos , México , Material Particulado/análisisRESUMEN
OBJECTIVES: Air pollution is a leading environmental risk, and socioeconomic status (SES) is postulated as an effect modifier, especially in children. There is a growing interest in exploring this modifier. The present manuscript reviews SES as an effect modifier in children's respiratory health. METHODS: A search in the PubMed and SCOPUS databases was conducted in September 2017 to identify studies with the inclusion criteria of being centred on children, respiratory outcomes, air pollutants and SES measurement. RESULTS: A total of 17 studies were included. Twelve used single SES variables, and the remaining studies included composite SES indices. Household income (9) and parental education (8) were frequently evaluated. The significance of the effect modifier was found in nine studies that demonstrated a higher risk for individuals living in a lower SES. Sources of heterogeneity included SES measurement, health outcomes and geographical aggregation. CONCLUSIONS: The results suggest a higher modification in the effect of SES, generally indicating greater risk for children in lower SES. Children's characteristics need to be more carefully theorized and measured in this area, including the use of transdisciplinary approaches.
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Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Salud Infantil/estadística & datos numéricos , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Trastornos Respiratorios/inducido químicamente , Clase Social , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , MasculinoRESUMEN
Exposure to air pollution particulate matter (PM) and tuberculosis (TB) are two of the leading global public health challenges affecting low and middle income countries. An estimated 4.26 million premature deaths are attributable to household air pollution and an additional 4.1 million to outdoor air pollution annually. Mycobacterium tuberculosis (M.tb) infects a large proportion of the world's population with the risk for TB development increasing during immunosuppressing conditions. There is strong evidence that such immunosuppressive conditions develop during household air pollution exposure, which increases rates of TB development. Exposure to urban air pollution has been shown to alter the outcome of TB therapy. Here we examined whether in vitro exposure to urban air pollution PM alters human immune responses to M.tb. PM2.5 and PM10 (aerodynamic diameters <2.5µm, <10µm) were collected monthly from rainy, cold-dry and warm-dry seasons in Iztapalapa, a highly populated TB-endemic municipality of Mexico City with elevated outdoor air pollution levels. We evaluated the effects of seasonality and size of PM on cytotoxicity and antimycobacterial host immunity in human peripheral blood mononuclear cells (PBMC) from interferon gamma (IFN-γ) release assay (IGRA)+ and IGRA- healthy study subjects. PM10 from cold-dry and warm-dry seasons induced the highest cytotoxicity in PBMC. With the exception of PM2.5 from the cold-dry season, pre-exposure to all seasonal PM reduced M.tb phagocytosis by PBMC. Furthermore, M.tb-induced IFN-γ production was suppressed in PM2.5 and PM10-pre-exposed PBMC from IGRA+ subjects. This observation coincides with the reduced expression of M.tb-induced T-bet, a transcription factor regulating IFN-γ expression in T cells. Pre-exposure to PM10 compared to PM2.5 led to greater loss of M.tb growth control. Exposure to PM2.5 and PM10 collected in different seasons differentially impairs M.tb-induced human host immunity, suggesting biological mechanisms underlying altered M.tb infection and TB treatment outcomes during air pollution exposures.
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Contaminantes Atmosféricos/toxicidad , Citotoxicidad Inmunológica/efectos de los fármacos , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/patogenicidad , Material Particulado/toxicidad , Adolescente , Adulto , Anciano , Ciudades , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Interacciones Microbiota-Huesped/efectos de los fármacos , Interacciones Microbiota-Huesped/inmunología , Humanos , Técnicas In Vitro , Interferón gamma/biosíntesis , Interleucina-1beta/biosíntesis , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Masculino , México , Persona de Mediana Edad , Mycobacterium tuberculosis/crecimiento & desarrollo , Tamaño de la Partícula , Fagocitosis/efectos de los fármacos , Estaciones del Año , Proteínas de Dominio T Box/inmunología , Salud Urbana , Adulto JovenRESUMEN
RATIONALE: Associations between urban (outdoor) airborne particulate matter (PM) exposure and TB and potential biological mechanisms are poorly explored. OBJECTIVES: To examine whether in vivo exposure to urban outdoor PM in Mexico City and in vitro exposure to urban outdoor PM2.5 (< 2.5 µm median aerodynamic diameter) alters human host immune cell responses to Mycobacterium tuberculosis. METHODS: Cellular toxicity (flow cytometry, proliferation assay (MTS assay)), M. tuberculosis and PM2.5 phagocytosis (microscopy), cytokine-producing cells (Enzyme-linked immune absorbent spot (ELISPOT)), and signalling pathway markers (western blot) were examined in bronchoalveolar cells (BAC) and peripheral blood mononuclear cells (PBMC) from healthy, non-smoking, residents of Mexico City (n=35; 13 female, 22 male). In vivo-acquired PM burden in alveolar macrophages (AM) was measured by digital image analysis. MEASUREMENTS AND MAIN RESULTS: In vitro exposure of AM to PM2.5 did not affect M. tuberculosis phagocytosis. High in vivo-acquired AM PM burden reduced constitutive, M. tuberculosis and PM-induced interleukin-1ß production in freshly isolated BAC but not in autologous PBMC while it reduced constitutive production of tumour necrosis factor-alpha in both BAC and PBMC. Further, PM burden was positively correlated with constitutive, PM, M. tuberculosis and purified protein derivative (PPD)-induced interferon gamma (IFN-γ) in BAC, and negatively correlated with PPD-induced IFN-γ in PBMC. CONCLUSIONS: Inhalation exposure to urban air pollution PM impairs important components of the protective human lung and systemic immune response against M. tuberculosis. PM load in AM is correlated with altered M. tuberculosis-induced cytokine production in the lung and systemic compartments. Chronic PM exposure with high constitutive expression of proinflammatory cytokines results in relative cellular unresponsiveness.
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Pulmón/inmunología , Mycobacterium tuberculosis/inmunología , Material Particulado/efectos adversos , Salud Urbana/estadística & datos numéricos , Adulto , Líquido del Lavado Bronquioalveolar/inmunología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/inmunología , Citocinas/biosíntesis , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Femenino , Citometría de Flujo/métodos , Interacciones Microbiota-Huesped/inmunología , Humanos , Mediadores de Inflamación/metabolismo , Masculino , México , Persona de Mediana Edad , Tamaño de la Partícula , Material Particulado/análisis , Material Particulado/farmacología , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , Adulto JovenRESUMEN
The Mexico City Metropolitan Area (MCMA) is one of the largest and most populated urban environments in the world and experiences high air pollution levels. To develop models that estimate pollutant concentrations at fine spatiotemporal scales and provide improved air pollution exposure assessments for health studies in Mexico City. We developed finer spatiotemporal land use regression (LUR) models for PM2.5, PM10, O3, NO2, CO and SO2 using mixed effect models with the Least Absolute Shrinkage and Selection Operator (LASSO). Hourly traffic density was included as a temporal variable besides meteorological and holiday variables. Models of hourly, daily, monthly, 6-monthly and annual averages were developed and evaluated using traditional and novel indices. The developed spatiotemporal LUR models yielded predicted concentrations with good spatial and temporal agreements with measured pollutant levels except for the hourly PM2.5, PM10 and SO2. Most of the LUR models met performance goals based on the standardized indices. LUR models with temporal scales greater than one hour were successfully developed using mixed effect models with LASSO and showed superior model performance compared to earlier LUR models, especially for time scales of a day or longer. The newly developed LUR models will be further refined with ongoing Mexico City air pollution sampling campaigns to improve personal exposure assessments.
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Contaminantes Atmosféricos/análisis , Contaminación del Aire/estadística & datos numéricos , Monitoreo del Ambiente/métodos , Ciudades , México , Material ParticuladoRESUMEN
OBJECTIVE: Children are recognized to be more susceptible than healthy adults to the effects of air pollution; however, relatively few Canadian studies of children have focused on industrial emissions. We conducted a spatial cross-sectional study to explore associations between emergency department (ED) visits for childhood asthma and residential proximity to two industrial sources of air pollution (coal-fired power plant and petrochemical industry) in Edmonton, Canada. METHODS: Using administrative health care data for Alberta between 2004 and 2010, we conducted a spatial analysis of disease clusters of count data around these two industrial sources. The distance from children's place of residence to these industrial sources was determined by using the six-character postal code from the children's ED visit. Clusters of cases were identified at the census dissemination area. Negative binomial multivariable spatial regression was used to estimate the risks of clusters in relation to the distance to these industrial sources. RESULTS: The relative risk of ED visits for asthma, calculated using a spatial scan test for events, was 10.4 (p value <0.01) within the power plant area when compared with the outside area. In addition, there was an inverse association of the distance to the power plant (coefficient = -0.01 per km) with asthma visits when multivariable models were used. No asthma clusters were identified around the petrochemical industrial area. CONCLUSION: Our analyses revealed that there was a cluster of ED visits for asthma among children who lived near the coal-fired power plant just outside Edmonton.
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Contaminación del Aire/estadística & datos numéricos , Asma/terapia , Servicio de Urgencia en Hospital/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos , Adolescente , Contaminación del Aire/efectos adversos , Asma/epidemiología , Canadá/epidemiología , Niño , Preescolar , Análisis por Conglomerados , Estudios Transversales , Femenino , Humanos , Industrias , Masculino , Riesgo , Análisis EspacialRESUMEN
In this review, we summarize and discuss the evidence regarding the interaction between air pollution, especially particulate matter (PM), and genomic instability. PM has been widely studied in the context of several diseases, and its role in lung carcinogenesis gained relevance due to an increase in cancer cases for which smoking does not seem to represent the main risk factor. According to epidemiological and toxicological evidence, PM acts as a carcinogenic factor in humans, inducing high rates of genomic alterations. Here, we discuss not only how PM is capable of inducing genomic instability during the carcinogenic process but also how our genetic background influences the response to the sources of damage.
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Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/estadística & datos numéricos , Carcinogénesis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Neoplasias Pulmonares/epidemiología , Material Particulado/toxicidad , Carcinógenos , Inestabilidad Genómica , Humanos , Pulmón/efectos de los fármacos , Neoplasias , Factores de Riesgo , FumarRESUMEN
Exposure to Particulate Matter (PM) could function as an adjuvant depending on the city of origin in mice allergic asthma models. Therefore, our aim was to determine whether inhalation of fine particles (PM2.5) from Mexico City could act as an adjuvant inducing allergic sensitization and/or worsening the asthmatic response in guinea pig, as a suitable model of human asthma. Experimental groups were Non-Sensitized (NS group), sensitized with Ovalbumin (OVA) plus Aluminum hydroxide (Al(OH)3) as adjuvant (S + Adj group), and sensitized (OVA) without adjuvant (S group). All the animals were exposed to Filtered Air (FA) or concentrated PM2.5 (5 h/daily/3 days), employing an aerosol concentrator system, PM2.5 composition was characterized. Lung function was evaluated by barometric plethysmography (Penh index). Inflammatory cells present in bronchoalveolar lavage were counted as well as OVA-specific IgG1 and IgE were determined by ELISA assay. Our results showed in sensitized animals without Al(OH)3, that the PM2.5 exposure (609 ± 12.73 µg/m3) acted as an adjuvant, triggering OVA-specific IgG1 and IgE concentration. Penh index increased â¼9-fold after OVA challenge in adjuvant-sensitized animals as well as in S + PM2.5 group (â¼6-fold), meanwhile NS + FA and S + FA lacked response. S + Adj + PM2.5 group showed an increase significantly of eosinophils and neutrophils in bronchoalveolar lavage. PM2.5 composition was made up of inorganic elements and Polycyclic Aromatic Hydrocarbons, as well as endotoxins and ß-glucan, all these components could act as adjuvant. Our study demonstrated that acute inhalation of PM2.5 acted as an adjuvant, similar to the aluminum hydroxide effect, triggering allergic asthma in a guinea pig model. Furthermore, in sensitized animals with aluminum hydroxide an enhancing influence of PM2.5 exposure was observed as specific-hyperresponsiveness to OVA challenge (quickly response) and eosinophilic and neutrophilic airway inflammation. Fine particles from Mexico City is a complex mix, which play a significant role as adjuvant in allergic asthma.
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Alérgenos/análisis , Asma , Modelos Animales , Material Particulado/análisis , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Animales , Líquido del Lavado Bronquioalveolar , Cobayas , Inmunoglobulina E , México , Ratones , Ratones Endogámicos BALB C , OvalbúminaRESUMEN
Airborne particulate matter with an aerodynamic diameter ≤10µm (PM10) is considered a risk factor for the development of lung cancer. Little is known about the cellular mechanisms by which PM10 is associated with cancer, but there is evidence that its exposure can lead to an acquired invasive phenotype, apoptosis evasion, inflammasome activation, and cytoskeleton remodeling in lung epithelial cells. Cytoskeleton remodeling occurs through actin stress fiber formation, which is partially regulated through ROCK kinase activation, we aimed to investigate if this protein was activated in response to PM10 exposure in A549 lung epithelial cells. Results showed that 10µg/cm2 of PM10 had no influence on cell viability but increased actin stress fibers, cytoplasmic ROCK expression, and phosphorylation of myosin phosphatase-targeting 1 (MYPT1) and myosin light chain (MLC) proteins, which are targeted by ROCK. The inhibition of ROCK prevented actin stress fiber formation and the phosphorylation of MYPT1 and MLC, suggesting that PM10 activated the ROCK-MYPT1-MLC pathway in lung epithelial cells. The activation of ROCK1 has been involved in the acquisition of malignant phenotypes, and its induction by PM10 exposure could contribute to the understanding of PM10 as a risk factor for cancer development through the mechanisms associated with invasive phenotype.
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Contaminantes Atmosféricos/toxicidad , Citoesqueleto/efectos de los fármacos , Cadenas Ligeras de Miosina/metabolismo , Fosfatasa de Miosina de Cadena Ligera/metabolismo , Material Particulado/toxicidad , Quinasas Asociadas a rho/metabolismo , Células A549 , Citoesqueleto/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Tamaño de la Partícula , Transducción de Señal , Fibras de Estrés/metabolismoRESUMEN
Atmospheric particulate matter with aerodynamic diameter ≤10 µm (PM10) is a risk factor for the development of lung cancer, but cellular pathways are not completely understood. STAT3 is a p21(Waf1/Cip1) transcription factor and is associated with proliferation and cell survival and is upregulated in lung cancer. PM10 exposure induces p21(Waf1/Cip1) expression, which could be related to STAT3 activation. The aims of this work were to investigate whether STAT3 was activated on lung epithelial cells after PM10 exposure and to determine whether or not STAT3 could have an impact on cell cycle distribution and cell survival. Our results showed that PM10 induced STAT3 activation through Src and PKCζ kinases, and it is partially responsible for the p21(Waf1/Cip1) induction that was also observed. Moreover, PM10 induced G1-G0 cell cycle arrest. The inhibition of STAT3 phosphorylation prevented cell cycle arrest and triggered apoptosis. These results suggest that PM10 exposure might activate a survival pathway related to STAT3 activation, similar to what has been described as part of the immune system and apoptosis evasion during tumor promotion and development.
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Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Pulmonares/etiología , Pulmón/efectos de los fármacos , Material Particulado/farmacología , Factor de Transcripción STAT3/metabolismo , Ciclo Celular/efectos de los fármacos , División Celular , Línea Celular Tumoral , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Humanos , Pulmón/citología , Pulmón/metabolismo , Neoplasias Pulmonares/metabolismo , Tamaño de la Partícula , Proteína Quinasa C/metabolismo , Activación Transcripcional , Familia-src Quinasas/metabolismoRESUMEN
Urban air pollution is a serious worldwide problem due to its impact on human health. In the past 60 years, growing evidence established a correlation between exposure to air pollutants and the developing of severe respiratory diseases. Recently particulate matter (PM) is drawing more public attention to various aspects including historical backgrounds, physicochemical characteristics, and its pathological role. Therefore, this review is focused on these aspects. The most famous air pollution disaster happened in London on December 1952; it has been calculated that more than 4,000 deaths occurred during this event. Air pollution is a complex mix of gases and particles. Gaseous pollutants disseminate deeply into the alveoli, allowing its diffusion through the blood-air barrier to several organs. Meanwhile, PM is a mix of solid or liquid particles suspended in the air. PM is deposited at different levels of the respiratory tract, depending on its size: coarse particles (PM10) in upper airways and fine particles (PM2.5) can be accumulated in the lung parenchyma, inducing several respiratory diseases. Additionally to size, the composition of PM has been associated with different toxicological outcomes on clinical and epidemiological, as well as in vivo and in vitro animal and human studies. PM can be constituted by organic, inorganic, and biological compounds. All these compounds are capable of modifying several biological activities, including alterations in cytokine production, coagulation factors balance, pulmonary function, respiratory symptoms, and cardiac function. It can also generate different modifications during its passage through the airways, like inflammatory cells recruitment, with the release of cytokines and reactive oxygen species (ROS). These inflammatory mediators can activate different pathways, such as MAP kinases, NF-κB, and Stat-1, or induce DNA adducts. All these alterations can mediate obstructive or restrictive respiratory diseases like asthma, COPD, pulmonary fibrosis, and even cancer. In 2013, outdoor air pollution was classified as Group 1 by IARC based on all research studies data about air pollution effects. Therefore, it is important to understand how PM composition can generate several pulmonary pathologies.
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BACKGROUND: Observed seasonal differences in particulate matter (PM) associations with human health may be due to their composition and to toxicity-related seasonal interactions. OBJECTIVES: We assessed seasonality in PM composition and in vitro PM pro-inflammatory potential using multiple PM samples. METHODS: We collected 90 weekly PM10 and PM2.5 samples during the rainy-warm and dry-cold seasons in five urban areas with different pollution sources. The elements, polycyclic aromatic hydrocarbons (PAHs), and endotoxins identified in the samples were subjected to principal component analysis (PCA). We tested the potential of the PM to induce tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) secretion in cultured human monocytes (THP-1), and we modeled pro-inflammatory responses using the component scores. RESULTS: PM composition varied by size and by season. PCA identified two main components that varied by season. Combustion-related constituents (e.g., vanadium, benzo[a]pyrene, benzo[a]anthracene) mainly comprised component 1 (C1). Soil-related constituents (e.g., endotoxins, silicon, aluminum) mainly comprised component 2 (C2). PM from the rainy-warm season was high in C2. PM (particularly PM2.5) from the dry-cold season was rich in C1. Elevated levels of cytokine production were associated with PM10 and C2 (rainy-warm season), whereas reduced levels of cytokine production were associated with PM2.5 and C1 (dry-cold season). TNFα secretion was increased following exposure to PM with high (vs. low) C2 content, but TNFα secretion in response to PM was decreased following exposure to samples containing ≥ 0.1% of C1-related PAHs, regardless of C2 content. The results of the IL-6 assays suggested more complex interactions between PM components and particle size. CONCLUSIONS: Variations in PM soil and PAH content underlie seasonal and PM size-related patterns in TNFα secretion. These results suggest that the mixture of components in PM explains some seasonal differences in associations between health outcomes and PM in epidemiologic studies. CITATION: Manzano-León N, Serrano-Lomelin J, Sánchez BN, Quintana-Belmares R, Vega E, Vázquez-López I, Rojas-Bracho L, López-Villegas MT, Vadillo-Ortega F, De Vizcaya-Ruiz A, Rosas Perez I, O'Neill MS, Osornio-Vargas AR. 2016. TNFα and IL-6 responses to particulate matter in vitro: variation according to PM size, season, and polycyclic aromatic hydrocarbon and soil content. Environ Health Perspect 124:406-412; http://dx.doi.org/10.1289/ehp.1409287.
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Contaminantes Atmosféricos/toxicidad , Interleucina-6/metabolismo , Material Particulado/toxicidad , Hidrocarburos Policíclicos Aromáticos/toxicidad , Estaciones del Año , Contaminantes del Suelo/toxicidad , Suelo/química , Factor de Necrosis Tumoral alfa/metabolismo , Contaminantes Atmosféricos/química , Línea Celular Tumoral , Ciudades , Endotoxinas/toxicidad , Monitoreo del Ambiente , Humanos , Metales/química , México , Tamaño de la Partícula , Material Particulado/química , Hidrocarburos Policíclicos Aromáticos/química , Contaminantes del Suelo/químicaRESUMEN
The PM10 airborne particulate matter with an aerodynamic diameter ≤10 µm is considered as a risk factor of various adverse health outcomes, including lung cancer. Here we described the sampling and composition of PM10 collected from an industrial zone (IZ), and a commercial zone (CZ) of Mexico City. The PM10 was collected with a high-volume sampler in the above mentioned locations and both types of PM10 sampled were characterized by the content of polycyclic aromatic hydrocarbons (PAHs), metals, and endotoxin. The endotoxin PM10 content from IZ and CZ displayed 138.4 UE/mg and 170.4 UE/mg of PM10, respectively.
RESUMEN
Airborne particulate matter with an aerodynamic diameter ≤ 10 µm (PM10) is a risk factor for the development of lung diseases and cancer. The aim of this work was to identify alterations in airway epithelial (A549) cells induced by PM10 that could explain how subtoxic exposure (10 µg/cm(2)) promotes a more aggressive in vitro phenotype. Our results showed that cells exposed to PM10 from an industrial zone (IZ) and an urban commercial zone (CZ) induced an increase in protease activity and invasiveness; however, the cell mechanism is different, as only PM10 from CZ up-regulated the activity of metalloproteases MMP-2 and MMP-9 and disrupted E-cadherin/ß-catenin expression after 48 h of exposure. These in vitro findings are relevant in terms of the mechanism action of PM10 in lung epithelial cells, which could be helpful in understanding the pathogenesis of some human illness associated with highly polluted cities.
Asunto(s)
Células Epiteliales/efectos de los fármacos , Pulmón/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Material Particulado/toxicidad , Contaminantes Atmosféricos/toxicidad , Antígenos CD , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Células Epiteliales/metabolismo , Humanos , Pulmón/citología , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Factores de Riesgo , Regulación hacia Arriba , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
UNLABELLED: Geostatistical interpolation methods to estimate individual exposure to outdoor air pollutants can be used in pregnancy cohorts where personal exposure data are not collected. Our objectives were to a) develop four assessment methods (citywide average (CWA); nearest monitor (NM); inverse distance weighting (IDW); and ordinary Kriging (OK)), and b) compare daily metrics and cross-validations of interpolation models. We obtained 2008 hourly data from Mexico City's outdoor air monitoring network for PM10, PM2.5, O3, CO, NO2, and SO2 and constructed daily exposure metrics for 1,000 simulated individual locations across five populated geographic zones. Descriptive statistics from all methods were calculated for dry and wet seasons, and by zone. We also evaluated IDW and OK methods' ability to predict measured concentrations at monitors using cross validation and a coefficient of variation (COV). All methods were performed using SAS 9.3, except ordinary Kriging which was modeled using R's gstat package. Overall, mean concentrations and standard deviations were similar among the different methods for each pollutant. Correlations between methods were generally high (r=0.77 to 0.99). However, ranges of estimated concentrations determined by NM, IDW, and OK were wider than the ranges for CWA. Root mean square errors for OK were consistently equal to or lower than for the IDW method. OK standard errors varied considerably between pollutants and the computed COVs ranged from 0.46 (least error) for SO2 and PM10 to 3.91 (most error) for PM2.5. OK predicted concentrations measured at the monitors better than IDW and NM. Given the similarity in results for the exposure methods, OK is preferred because this method alone provides predicted standard errors which can be incorporated in statistical models. The daily estimated exposures calculated using these different exposure methods provide flexibility to evaluate multiple windows of exposure during pregnancy, not just trimester or pregnancy-long exposures. IMPLICATIONS: Many studies evaluating associations between outdoor air pollution and adverse pregnancy outcomes rely on outdoor air pollution monitoring data linked to information gathered from large birth registries, and often lack residence location information needed to estimate individual exposure. This study simulated 1,000 residential locations to evaluate four air pollution exposure assessment methods, and describes possible exposure misclassification from using spatial averaging versus geostatistical interpolation models. An implication of this work is that policies to reduce air pollution and exposure among pregnant women based on epidemiologic literature should take into account possible error in estimates of effect when spatial averages alone are evaluated.
Asunto(s)
Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Exposición a Riesgos Ambientales , Monitoreo del Ambiente/métodos , Modelos Estadísticos , Femenino , Humanos , México , Embarazo , Estaciones del AñoRESUMEN
The carcinogenic potential of urban particulate matter (PM) has been partly attributed to polycyclic aromatic hydrocarbons (PAHs) content, which activates the aryl hydrocarbon receptor (AhR). Here we report the effect of PM with an aerodynamic size of 10 µm (PM10) on the induction of AhR pathway in A549 cells, evaluating its downstream targets CYP1B1, IL-6, IL-8 and c-Jun. Significant increases in CYP1B1 protein and enzyme activity; IL-6 and IL-8 secretion and c-Jun protein were found in response to PM10. The formation of PAH-DNA adducts was also detected. The involvement of AhR pathway was confirmed with Resveratrol as AhR antagonist, which reversed CYP1B1 and c-Jun induction. Nevertheless, in IL-6 and IL-8 secretion, the Resveratrol was ineffective, suggesting an effect independent of this pathway. Considering the role of c-Jun in oncogenesis, its induction by PM may be contributing to its carcinogenic potential through induction of AhR pathway by PAHs present in PM10.