Diesel exhaust particles induce CYP1A1 and pro-inflammatory responses via differential pathways in human bronchial epithelial cells

<p>Abstract</p> <p>Background</p> <p>Exposure to diesel engine exhaust particles (DEPs) has been associated with several adverse health outcomes in which inflammation seems to play a key role. DEPs contain a range of different inorganic and organic compounds, including polycyclic aromatic hydrocarbons (PAHs). During the metabolic activation of PAHs, CYP1A1 enzymes are known to play a critical role. In the present study we investigated the potential of a characterised sample of DEPs to induce cytotoxicity, to influence the expression of CYP1A1 and inflammation-related genes, and to activate intracellular signalling pathways, in human bronchial epithelial cells. We specifically investigated to what extent DEP-induced expression of interleukin (IL)-6, IL-8 and cyclooxygenase (COX)-2 was regulated differentially from DEP-induced expression of CYP1A1.</p> <p>Results</p> <p>The cytotoxicity of the DEPs was characterised by a marked time- and concentration-dependent increase in necrotic cells at 4 h and above 200 μg/ml (~ 30 μg/cm²). DEP-induced DNA-damage was only apparent at high concentrations (≥ 200 μg/ml). IL-6, IL-8 and COX-2 were the three most up-regulated genes by the DEPs in a screening of 20 selected inflammation-related genes. DEP-induced expression of CYP1A1 was detected at very low concentrations (0.025 μg/ml), compared to the expression of IL-6, IL-8 and COX-2 (50-100 μg/ml). A CYP1A1 inhibitor (α-naphthoflavone), nearly abolished the DEP-induced expression of IL-8 and COX-2. Of the investigated mitogen-activated protein kinases (MAPKs), the DEPs induced activation of p38. A p38 inhibitor (SB202190) strongly reduced DEP-induced expression of IL-6, IL-8 and COX-2, but only moderately affected the expression of CYP1A1. The DEPs also activated the nuclear factor-κB (NF-κB) pathway, and suppression by siRNA tended to reduce the DEP-induced expression of IL-8 and COX-2, but not CYP1A1.</p> <p>Conclusion</p> <p>The present study indicates that DEPs induce both CYP1A1 and pro-inflammatory responses in vitro, but via differential intracellular pathways. DEP-induced pro-inflammatory responses seem to occur via activation of NF-κB and p38 and are facilitated by CYP1A1. However, the DEP-induced CYP1A1 response does not seem to involve NF-κB and p38 activation. Notably, the present study also indicates that expression of CYP1A1 may represent a particular sensitive biomarker of DEP-exposure.</p

IL-1beta differently involved in IL-8 and FGF-2 release in crystalline silica-treated lung cell co-cultures

<p>Abstract</p> <p>Background</p> <p>Inhalation of crystalline silica particles is in humans associated with inflammation and development of fibrosis. The aim of the present study was to investigate the effect of crystalline silica on the release of the fibrosis- and angiogenesis-related mediator FGF-2 and the pro-inflammatory mediator IL-8, and how IL-1β and TNF-α were involved in this release from various mono- and co-cultures of monocytes, pneumocytes and endothelial cells.</p> <p>Results</p> <p>Silica exposure induced an increase of IL-8 release from monocytes and from pneumocytes alone, and the FGF-2 level in the medium increased upon silica exposure of pneumocytes. Both the responses were enhanced in non-contact co-cultures with endothelial cells. The FGF-2 release seemed to increase with the silica-induced decrease in the number of pneumocytes. The release of IL-8 and FGF-2 was partially suppressed in cultures with pneumocytes in contact with monocytes compared to non-contact cultures. Treatment with anti-TNF-α and the IL-1 receptor antagonist revealed that release of IL-1β, and not TNF-α, from monocytes dominated the regulation of IL-8 release in co-cultures. For release of FGF-2, IL-1ra was without effect. However, exogenous IL-1β reduced the FGF-2 levels, strongly elevated the FGF-2-binding protein PTX3, and prevented the reduction in the number of pneumocytes induced by silica.</p> <p>Conclusion</p> <p>IL-1β seems to be differently involved in the silica-induced release of IL-8 and FGF-2 in different lung cell cultures. Whereas the silica-induced IL-8 release is regulated via an IL-1-receptor-mediated mechanism, IL-1β is suggested only indirectly to affect the silica-induced FGF-2 release by counteracting pneumocyte loss. Furthermore, the enhanced IL-8 and FGF-2 responses in co-cultures involving endothelial cells show the importance of the interaction between different cell types and may suggest that both these mediators are important in angiogenic or fibrogenic processes.</p

Physicochemical characterisation of combustion particles from vehicle exhaust and residential wood smoke

BACKGROUND: Exposure to ambient particulate matter has been associated with a number of adverse health effects. Particle characteristics such as size, surface area and chemistry seem to influence the negative effects of particles. In this study, combustion particles from vehicle exhaust and wood smoke, currently used in biological experiments, were analysed with respect to microstructure and chemistry. METHODS: Vehicle exhaust particles were collected in a road tunnel during two seasons, with and without use of studded tires, whereas wood smoke was collected from a stove with single-stage combustion. Additionally, a reference diesel sample (SRM 2975) was analysed. The samples were characterised using transmission electron microscopy techniques (TEM/HRTEM, EELS and SAED). Furthermore, the elemental and organic carbon fractions were quantified using thermal optical transmission analysis and the content of selected PAHs was determined by gas chromatography-mass spectrometry. RESULTS: Carbon aggregates, consisting of tens to thousands of spherical primary particles, were the only combustion particles identified in all samples using TEM. The tunnel samples also contained mineral particles originating from road abrasion. The geometric diameters of primary carbon particles from vehicle exhaust were found to be significantly smaller (24 ± 6 nm) than for wood smoke (31 ± 7 nm). Furthermore, HRTEM showed that primary particles from both sources exhibited a turbostratic microstructure, consisting of concentric carbon layers surrounding several nuclei in vehicle exhaust or a single nucleus in wood smoke. However, no differences were detected in the graphitic character of primary particles from the two sources using SAED and EELS. The total PAH content was higher for combustion particles from wood smoke as compared to vehicle exhaust, whereas no source difference was found for the ratio of organic to total carbon. CONCLUSION: Combustion particles from vehicle exhaust and residential wood smoke differ in primary particle diameter, microstructure, and PAH content. Furthermore, the analysed samples seem suitable for assessing the influence of physicochemical characteristics of particles on biological responses

Cytokine release from alveolar macrophages exposed to ambient particulate matter: Heterogeneity in relation to size, city and season

BACKGROUND: Several studies have demonstrated an association between exposure to ambient particulate matter (PM) and respiratory and cardiovascular diseases. Inflammation seems to play an important role in the observed health effects. However, the predominant particle component(s) that drives the inflammation is still not fully clarified. In this study representative coarse (2.5–10 μm) and fine (0.1–2.5 μm) particulate samples from a western, an eastern, a northern and a southern European city (Amsterdam, Lodz, Oslo and Rome) were collected during three seasons (spring, summer and winter). All fractions were investigated with respect to cytokine-inducing potential in primary macrophages isolated from rat lung. The results were related to the physical and chemical parameters of the samples in order to disclose possible connections between inflammatory potential and specific characteristics of the particles. RESULTS: Compared on a gram-by gram basis, both site-specific and seasonal variations in the PM-induced cytokine responses were demonstrated. The samples collected in the eastern (Lodz) and southern (Rome) cities appeared to be the most potent. Seasonal variation was most obvious with the samples from Lodz, with the highest responses induced by the spring and summer samples. The site-specific or seasonal variation in cytokine release could not be attributed to variations in any of the chemical parameters. Coarse fractions from all cities were more potent to induce the inflammatory cytokines interleukin-6 and tumour necrosis factor-α than the corresponding fine fractions. Higher levels of specific elements such as iron and copper, some polycyclic aromatic hydrocarbons (PAHs) and endotoxin/lipopolysaccaride seemed to be prevalent in the coarse fractions. However, variations in the content of these components did not reflect the variation in cytokine release induced by the different coarse fractions. Addition of polymyxin B did not affect the particle-induced cytokine release, indicating that the variations in potency among the coarse fractions are not explained by endootoxin. CONCLUSION: The inflammatory potential of ambient PM demonstrated heterogeneity in relation to city and season. The coarse particle fractions were consistently more potent than the respective fine fractions. Though a higher level of some elements, PAH and endotoxin was found in the coarse fractions, the presence of specific components was not sufficient to explain all variations in PM-induced cytokine release

Do Carpets Impair Indoor Air Quality and Cause Adverse Health Outcomes: A Review

Several earlier studies have shown the presence of more dust and allergens in carpets compared with non-carpeted floors. At the same time, adverse effects of carpeted floors on perceived indoor air quality as well as worsening of symptoms in individuals with asthma and allergies were reported. Avoiding extensive carpet use in offices, schools, kindergartens and bedrooms has therefore been recommended by several health authorities. More recently, carpet producers have argued that former assessments were obsolete and that modern rugs are unproblematic, even for those with asthma and allergies. To investigate whether the recommendation to be cautious with the use of carpets is still valid, or whether there are new data supporting that carpet flooring do not present a problem for indoor air quality and health, we have reviewed the literature on this matter. We have not found updated peer reviewed evidence that carpeted floor is unproblematic for the indoor environment. On the contrary, also more recent data support that carpets may act as a repository for pollutants which may become resuspended upon activity in the carpeted area. Also, the use of carpets is still linked to perception of reduced indoor air quality as well as adverse health effects as previously reported. To our knowledge, there are no publications that report on deposition of pollutants and adverse health outcomes associated with modern rugs. However, due to the three-dimensional structure of carpets, any carpet will to some extent act like a sink. Thus, continued caution should still be exercised when considering the use of wall-to-wall carpeted floors in schools, kindergartens and offices, as well as in children’s bedrooms unless special needs indicate that carpets are preferableAcknowledgments: This study has not received any funding or grants. NIPH cover the costs for publishing in open access.publishedVersio

Health effects of residential wood smoke particles: the importance of combustion conditions and physicochemical particle properties

Background: Residential wood combustion is now recognized as a major particle source in many developed countries, and the number of studies investigating the negative health effects associated with wood smoke exposure is currently increasing. The combustion appliances in use today provide highly variable combustion conditions resulting in large variations in the physicochemical characteristics of the emitted particles. These differences in physicochemical properties are likely to influence the biological effects induced by the wood smoke particles. Outline: The focus of this review is to discuss the present knowledge on physicochemical properties of wood smoke particles from different combustion conditions in relation to wood smoke-induced health effects. In addition, the human wood smoke exposure in developed countries is explored in order to identify the particle characteristics that are relevant for experimental studies of wood smoke-induced health effects. Finally, recent experimental studies regarding wood smoke exposure are discussed with respect to the applied combustion conditions and particle properties. Conclusion: Overall, the reviewed literature regarding the physicochemical properties of wood smoke particles provides a relatively clear picture of how these properties vary with the combustion conditions, whereas particle emissions from specific classes of combustion appliances are less well characterised. The major gaps in knowledge concern; (i) characterisation of the atmospheric transformations of wood smoke particles, (ii) characterisation of the physicochemical properties of wood smoke particles in ambient and indoor environments, and (iii) identification of the physicochemical properties that influence the biological effects of wood smoke particles

Future air quality and related health effects in a Nordic perspective : the possible impacts of future changes in climate, anthropogenic emissions, demography and building structure

Air pollution has been estimated to lead to ca. 10.000 premature deaths every year in the Nordic countries. The external costs related to the health effects of air pollution amounts to EUR 8-13 billion per year. Main drivers, such as changes in climate, anthropogenic emissions, building structure and demography have a vast impact on air quality-related effects on human health. The purpose of the FutureAirNordic project has been to investigate how potential future changes in main drivers will impact the assessment of air quality-related human health effects. Estimations of premature mortality due to exposure to air pollution as well as the external costs associated with the negative health effects have been analyzed. The results can contribute to improved assessments under future conditions and can be used to evaluate how policies and regulations impact the health effects of air pollution

Future Premature Mortality Due to O3, Secondary Inorganic Aerosols and Primary PM in Europe — Sensitivity to Changes in Climate, Anthropogenic Emissions, Population and Building Stock

Air pollution is an important environmental factor associated with health impacts in Europe and considerable resources are used to reduce exposure to air pollution through emission reductions. These reductions will have non-linear effects on exposure due, e.g., to interactions between climate and atmospheric chemistry. By using an integrated assessment model, we quantify the effect of changes in climate, emissions and population demography on exposure and health impacts in Europe. The sensitivity to the changes is assessed by investigating the differences between the decades 2000–2009, 2050–2059 and 2080–2089. We focus on the number of premature deaths related to atmospheric ozone, Secondary Inorganic Aerosols and primary PM. For the Nordic region we furthermore include a projection on how population exposure might develop due to changes in building stock with increased energy efficiency. Reductions in emissions cause a large significant decrease in mortality, while climate effects on chemistry and emissions only affects premature mortality by a few percent. Changes in population demography lead to a larger relative increase in chronic mortality than the relative increase in population. Finally, the projected changes in building stock and infiltration rates in the Nordic indicate that this factor may be very important for assessments of population exposure in the future