Airborne Particulate Matter Exposure Research Articles

Polycyclic aromatic hydrocarbon (PAH) activation of AhR inhibits glutathione S-transferase (GST) activity in primary human small airway epithelial cells (hSAECs)

Background: PAH represents the organic phase of particulate matter (PM) in air pollution emitted via the incomplete combustion of various compounds (i.e. diesel fuel, wood, and plastics). It is widely regarded that PAH activation of aryl hydrocarbon receptor (AhR) plays an important role in pro-inflammatory signaling, however the mechanisms remain unknown. In contrast- endogenous AhR agonists, such as 6-Formylindolo[3,2-b]carbazole (FICZ), exert pleiotropic protective effects against inflammation, fibrosis, and oxidative stress. The objective of our research program is to delineate the differences between activation of AhR by PAH (with adverse effects) compared to its beneficial homeostatic activation by endogenous FICZ. PM may induce oxidative stress in part through inhibition of antioxidant defense mechanisms. GSTs are a superfamily of enzymes that plays an important role in protecting cells from oxidative damage (by conjugating reduced glutathione to substrates under pro-oxidizing conditions). We hypothesize that PAH activation of AhR contributes to oxidative stress via inhibition of GST activity in primary hSAECs. Methods: Primary hSAECs were subjected to varying dosages of PAH [0, 250, 500, 1000, 5000 ng/mL] to model airborne PM exposure levels, and to increasing doses of FICZ [0, 0.50, 10, 100, 1000 nM] to model normal and excessively high endogenous ligand activation of AhR. We determined the relative potencies of PAH and FICZ by measuring CYP1A1 and CYP1B1 gene expression. Oxidative stress was measured using DHE-labeling and GST activity was measured with enzymatic kits (Sigma Aldrich). AhR activity was pharmacologically inhibited using 10μM CH223191. Statistical analysis was conducted using SigmaPlot 14.0 (Systat Software). Results: PAH and FICZ maximally stimulate hSAEC CYP1A1 and CYP1B1 expression at 1000ng/mL and 100nM, respectively, and are therefore defined as equipotent concentrations used in our studies. In a representative experiment in hSAECs, PAH (1000ng/mL) significantly increased hSAEC oxidative stress vs FICZ (100nM) n=6, p<0.01), while significantly decreasing GST specific activity vs equipotent FICZ activation of AhR in primary hSAECs from a 66-year-old female without lung disease (26.6±0.874 vs 28.3±.611 nmol/mL/min); n=6 from 2 independent assays; p=0.032. Similar differential effects of PAH vs FICZ activation of AhR on GST were seen in additional experiments with male hSAECs and Calu-3 cells (male). Importantly, CH223191 inhibition of GST enzymatic activity suggests that AhR plays an important role in protecting cells from oxidative stress. Conclusions: Our studies indicate that airborne PAH exposure can have detrimental health effects on the lung via aberrant AhR signaling. Significance: Understanding activity of AhR signaling can leads to novel therapeutic options for redox disorders in the lung. Funding: VA 5I01BX001777-05 (RP) and R01HL137033 (MH). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Omics-based cutting-edge technologies for identifying predictive biomarkers to measure the impact of air borne particulate matter exposure on male reproductive health

The reproductive lifespan of an individual is a critical determinant of their health, population dynamics, and aging. Research has established a clear association between environmental air pollution, particulate matter (PM), and reproductive health. Recent studies have focused on the impact of air pollution on male reproductive health. Chronic or acute exposure to airborne PM0.1, PM2.5, and PM10 has been found to trigger mitochondrial oxidative stress, double-strand DNA breaks, epigenetic modifications, and endocrine disruption in male reproductive tract functions. Consequently, identifying and validating PM-associated predictive biomarkers, including genes, transcripts, epimutations, proteins, and metabolites, hold promise for improving male reproductive efficiency. Omics-based techniques, such as next-generation sequencing, comparative genomic hybridization, genome-wide association studies, single-cell RNA sequencing, microarray analysis, mass spectroscopy, 2D gel electrophoresis, Raman spectroscopy, near-infrared spectroscopy, and nuclear magnetic resonance, have provided crucial insights into the pathological mechanisms underlying air pollution-related male reproductive health issues. This article presents a comprehensive assessment of existing evidence in this field, offering a methodical examination of findings that hold immense potential for addressing the adverse effects of air pollution on male reproductive health.

Impact of airborne particulate matter exposure on hospital admission for Alzheimer's disease and the attributable economic burden: evidence from a time-series study in Sichuan, China

BackgroundAlzheimer's disease (AD) and other forms of dementia are the seventh leading cause of death. Studies discern the inclusion of air pollution among modifiable risk factors for dementia, while limited studies are for China. This study aims to examine the short-term association between airborne particulate matter (PM) and the hospitalizations of AD, including the economic costs in China.MethodsA total of 4975 cases of AD patients hospitalized from 2017 to 2019, were collected from nine city and 411 medical institutions in Sichuan Province, China. Data on air pollutants such as PM2.5, PM10, and NO2 were obtained from 183 air quality monitoring stations in Sichuan Province. A time series-generalized additive model was used to estimate the association between short-term exposure to PM (lag1–lag7 and moving average lag01–lag07) and AD hospital admissions (HAs), stratified by gender, age, and season.ResultsPositive short-term exposure to airborne PM was found for the HAs of AD. The greatest effect on the number of AD inpatients was on single-day lag1 (PM2.5:1.034 (95% confidence interval (CI) 1.011, 1.058)). The association was also significant in the two-pollutant model. In the study period, 16.48% of AD HAs were attributed to the effect of PM. The total economic costs of AD attributable to PM exposure were US$ 2.56 million, including US$ 2.25 million of direct medical costs and US$ 0.31 million of indirect economic costs.ConclusionsThis study suggests that short-term exposure to airborne PM may increase the risk of AD HAs in Sichuan Province and result in associated economic costs.

Airborne particulate matter exposure impairs lung redox metabolism involved in tissue damage repair mechanisms

Airborne particulate matter exposure impairs lung redox metabolism involved in tissue damage repair mechanisms

Airborne particulate matter exposure impairs lung redox metabolism involved in tissue damage repair mechanisms

Airborne particulate matter exposure impairs lung redox metabolism involved in tissue damage repair mechanisms

Cell-free circulating mitochondrial DNA: An emerging biomarker for airborne particulate matter associated with cardiovascular diseases.

The association of airborne particulate matter exposure with the deteriorating function of the cardiovascular system is fundamentally driven by the impairment of mitochondrial-nuclear crosstalk orchestrated by aberrant redox signaling. The loss of delicate balance in retrograde communication from mitochondria to the nucleus often culminates in the methylation of the newly synthesized strand of mitochondrial DNA (mtDNA) through DNA methyl transferases. In highly metabolic active tissues such as the heart, mtDNA's methylation state alteration impacts mitochondrial bioenergetics. It affects transcriptional regulatory processes involved in biogenesis, fission, and fusion, often accompanied by the integrated stress response. Previous studies have demonstrated a paradoxical role of mtDNA methylation in cardiovascular pathologies linked to air pollution. A pronounced alteration in mtDNA methylation contributes to systemic inflammation, an etiological determinant for several co-morbidities, including vascular endothelial dysfunction and myocardial injury. In the current article, we evaluate the state of evidence and examine the considerable promise of using cell-free circulating methylated mtDNA as a predictive biomarker to reduce the more significant burden of ambient air pollution on cardiovascular diseases.

The links of fine airborne particulate matter exposure to occurrence of cardiovascular and metabolic diseases in Michigan, USA.

Air pollutants, particularly airborne particulate matter with aerodynamic diameter < 2.5μm (PM2.5), have been linked to the increase in mortality and morbidity associated with cardiovascular and metabolic diseases. In this study, we investigated the dose-risk relationships between PM2.5 concentrations and occurrences of cardiovascular and metabolic diseases as well as the confounding socioeconomic factors in Michigan, USA, where PM2.5 levels are generally considered acceptable. Multivariate linear regression analyses were performed to investigate the relationship between health outcome and annual ground-level PM2.5 concentrations of 82 counties in Michigan. The analyses revelated significant linear dose-response associations between PM2.5 concentrations and cardiovascular disease (CVD) hospitalization. A 10 μg/m3 increase in PM2.5 exposure was found to be associated with a 3.0% increase in total CVD, 0.45% increase in Stroke, and a 0.3% increase in Hypertension hospitalization rates in Medicare beneficiaries. While the hospitalization rates of Total Stroke, Hemorrhagic Stroke, and Hypertension in urbanized counties were significantly higher than those of rural counties, the death rates of coronary heart disease and ischemic stroke in urbanized counties were significantly lower than those of rural counties. These results were correlated with the facts that PM2.5 levels in urbanized counties were significantly higher than that in rural counties and that the percentage of the population with health insurance and the median household income in rural counties were significantly lower. While obesity prevalence showed evidence of a weak positive correlation (ρ = 0.20, p-value = 0.078) with PM2.5 levels, there was no significant dose-response association between county diabetes prevalence rates and PM2.5 exposure in Michigan. In summary, this study revealed strong dose-response associations between PM2.5 concentrations and CVD incidence in Michigan, USA. The socioeconomic factors, such as access to healthcare resources and median household income, represent important confounding factors that could override the impact of PM2.5 exposure on CVD mortality.

Brain Accumulation and Toxicity Profiles of Silica Nanoparticles: The Influence of Size and Exposure Route

Nanoparticles (NPs) can make their way to the brain and cause in situ damage, which is a concern for nanomaterial application and airborne particulate matter exposure. Our recent study indicated that respiratory exposure to silica nanoparticles (SiO2 NPs) caused unexpected cardiovascular toxic effects. However, the toxicities of SiO2 NPs in other organs have warranted further investigation. To confirm the accumulation of SiO2 NPs in the brain, we introduced SiO2 NPs with different diameters into mice via intranasal instillation (INI) and intravenous injection (IVI) in parallel. We found that SiO2 NPs may target the brain through both olfactory and systemic routes, but the size of SiO2 NPs and delivery routes both significantly affected their brain accumulation. Surprisingly, while equivalent SiO2 NPs were found in the brain regions, brain lesions were distinctly much higher in INI than in the IVI group. Mechanistically, we showed that SiO2 NPs introduced via INI induced brain apoptosis and autophagy, while the SiO2 NPs introduced via IVI only induced autophagy in the brain.

The Gut Microbiome is Significantly Altered in APP/PS1 Mice Following Air Particulate Matter Exposure

The detrimental effects of air pollution extend beyond its pathological cardiovascular and pulmonary consequences. Recent research has implicated exposure of air pollution, specifically air particulate matter (PM2.5, &lt;2.5 μm diameter), in Alzheimer’s disease (AD) development, though the pathogenesis remains unknown. Gut dysbiosis (i.e., alterations of gut microbiota resident bacterial populations) can result from dietary changes, stress, medications, particulate matter exposure, and alcohol or chemical consumption. Unbalanced bacterial populations may resolve themselves, though persistent stressors can induce chronic dysbiosis, which is implicated in the development of inflammatory bowel disease, obesity, diabetes, cancer, and AD. Thus, we hypothesized that PM2.5 contributes to gut dysbiosis and detrimental microbial byproducts that may ultimately accelerate AD progression in a transgenic AD mouse model. We tested our hypothesis by subjecting 3‐month‐old AD transgenic (APP/PS1) and non‐carrier wildtype (WT) male mice to filtered air (FA) or PM2.5 exposure for 5 days/week, 6 hours/day for 3 months (n=9‐12). The average daily PM exposure is 90.0 μg/m3, which is a 5‐fold concentration above the ambient mean daily PM2.5 concentration (18.8 ±11.4 μg/m3) at the study site in Columbus, OH. The composition has been previously examined and was found to contain high levels of zinc and iron. Following the 3‐month exposure, fecal samples were collected, and DNA was isolated before 16S Illumina sequencing was performed. Sequencing was implemented to determine gut microbial changes associated with genotype and exposure conditions. This data revealed significant alterations in beta diversity based on genotype and exposure, representing altered bacterial communities associated with experimental conditions (Analysis of Molecular Variance (AMOVA), p&lt;0.001)). Additionally, PM2.5 exposure increased gut microbial alpha diversity for both APP/PS1 and WT mice (Shannon‐Weiner diversity, p&lt;0.05). Taken together, these findings indicate that airborne particulate matter exposure induces gut microbiota changes and contributes to microbial dysfunction in a transgenic mouse model of AD.

Air Particulate Matter Significantly Alters Bacterial‐Derived Metabolites in APP/PS1 Mice

Alterations to gastrointestinal bacterial communities have been linked to the exacerbation of numerous diseases, including Alzheimer’s Disease (AD), via changes to bacterial‐derived metabolites. Community changes can result from antibiotic use, dietary changes, psychosocial stress, and possibly air particulate matter exposure. Previous studies from our group demonstrated that a transgenic mouse model predisposed to create amyloid‐β fibers similar to AD, namely APP/PS1 mice, exposed to air particulate matter (PM) led to significant increases in hippocampal amyloid‐β1‐40 (Aβ) and Aβ1‐42, as well as astrocytosis, microgliosis, and proinflammatory cytokines in the temporal cortex as compared to PM‐exposed non‐carrier mice. Such findings indicate the presence of PM2.5‐induced neuroinflammation in APP/PS1 mice; however, the mechanism by which this occurs is unknown. Recent data demonstrates PM‐induced alterations to the gut microbiome, prompting us to test the hypothesis that disruptions of microbial‐derived metabolites are present in PM‐exposed APP/PS1 mice. To test this hypothesis, APP/PS1 and non‐carrier, littermate wild type (WT) mice were exposed to filtered air (FA) or PM for 5 days/week, 6 hours/day, for 3 months. The average daily PM exposure is 90.0 μg/m3, which is a 5‐fold concentration above the ambient mean daily PM2.5 concentration (18.8 ±11.4 μg/m3) at the study site in Columbus, OH. At the end of the 3‐month exposure, fecal samples were collected to assess bacterial byproducts, i.e. short chain fatty acids (SCFAs), by gas chromatography/mass spectrometry. Serum samples were collected to characterize additional metabolites including the bacterial metabolite trimethylamine (TMA) by liquid chromatography/mass spectrometry. Results demonstrated that SCFA butyric acid was significantly reduced by PM‐exposure in both APP/PS1 and WT animals as compared to their FA‐exposed counterparts (p&lt;0.01) and propionic acid was significantly increased in FA‐exposed APP/PS1 mice as compared to their WT counterparts (p&lt;0.0001). Serum metabolite analyses revealed distinct principal component patterns among groups, demonstrating unique metabolic profiles associated with exposure and genotype. One such metabolite, TMA, was significantly increased by PM‐exposure (p&lt;0.05). Taken together, these findings indicate that airborne particulate matter exposure alters metabolic profiles in a transgenic mouse model of AD.

Integrated mitoepigenetic signalling mechanisms associated with airborne particulate matter exposure: A cross-sectional pilot study

Airborne particulate matter (PM) is known to be associated with various chronic human ailments, however, precise underlying molecular mechanisms remains elusive. Based on the place of residence and amount of PM exposure, the study groups were divided into high-risk group and low-risk group. Different parameters related to oxidative DNA damage and repair, integrated stress response, mito-nuclear crosstalk, mitochondrial biogenesis, functioning and epigenetic machinery were assessed. The results of our pilot study showed that in comparison to the low-risk group, the levels of mitochondrial stress and oxidative DNA damage were significantly higher in the high-risk group. In addition, the upregulated expression levels of OMA1, DELE1, and HRI genes in the high-risk group confirmed the onset of an integrated stress response. These disturbances in the mitochondrial genome were further found to be associated with the vital processes of mitochondrial biogenesis. The high-risk group reported significant alterations in the mtDNA copy number and expression of mitochondrial fission and fusion genes. Importantly, we also observed higher expression levels of mitochondrial transcription factor TFAM, a key regulator of mtDNA replication and transcription in the high-risk group. Moreover, these changes were accompanied by the disturbances in the expression of TET genes and levels of mtDNA methylation. This impaired mtDNA methylation profile further correlated with the disturbed activity of electron chain complexes and expression of the mitochondria function genes in the high-risk group. Altogether, our observations provide vital molecular insights of the integrated mitoepigenetic signalling network in the airborne PM exposed individuals, hitherto unreported.

Abstract P391: Inhalation Of Airborne Particulate Matter Alters Cardiovascular Function Of Alzheimer-prone Mice

Air pollution has detrimental effects on cardiovascular and lung function, and the extent of its pathological consequences continues to be uncovered. Recently, air pollution has been implicated in the development of Alzheimer Disease (AD) progression. AD and heart failure are common co-morbidities, giving reason to believe that cardiovascular dysfunction may contribute to AD. A known contributor to cardiovascular dysfunction-particulate matter (PM 2.5 , &lt; 2.5 μm diameter)—is a critical component of air pollution and is considered a risk factor for heart failure and AD development. This co-morbidity pattern and shared environmental risk factor prompted the hypothesis that PM 2.5 contributes to cardiovascular dysfunction in a transgenic mouse model of AD. We tested our hypothesis by subjecting 6-month-old transgenic (APP) and non-carrier wildtype (WT) male mice to filtered air (FA) or PM 2.5 for 5 days/week, 6 hours/day for 3 months (n = 34). Following exposure, echocardiography, pressure-volume (PV) loops, and respiratory mechanics were performed to detect cardiac and pulmonary changes associated with genotype and exposure conditions among the 3-month group. Echocardiography revealed left ventricular anterior wall thickness in systole was significantly elevated among PM-exposed APP mice compared to FA-exposed APP controls. PV data demonstrated significant reduced end-systolic elastance in PM-exposed mice compared to FA-exposed mice in both WT and APP mouse models, demonstrating impaired contractility. PV loops also showed that the time constant of isovolumetric relaxation was increased in PM-exposed compared to FA-exposed WT mice. APP mice experienced higher lung resistance and central airway resistance with an increasing dose of methacholine. Taken together, these findings indicate airborne particulate matter exposure causes cardiac and pulmonary dysfunction in a transgenic mouse model of AD.

Systems level insights into the impact of airborne exposure on SARS-CoV-2 pathogenesis and COVID-19 outcome – A multi-omics big data study

Coronavirus disease 2019 (COVID-19) is a viral pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that led to more than 800,00 deaths and continues to be a major threat worldwide. The scientific community has been studying the risk factors associated with SARS-CoV-2 infection and pathogenesis. Recent studies highlight the possible contribution of atmospheric air pollution, specifically particulate matter (PM) exposure as a co-factor in COVID-19 severity. Hence, meaningful translation of suitable omics datasets of SARS-CoV-2 infection and PM exposure is warranted to understand the possible involvement of airborne exposome on COVID-19 outcome. Publicly available transcriptomic data (microarray and RNA-Seq) related to COVID-19 lung biopsy, SARS-CoV-2 infection in epithelial cells and PM exposure (lung tissue, epithelial and endothelial cells) were obtained in addition with proteome and interactome datasets. System-wide pathway/network analysis was done through appropriate software tools and data resources. The primary findings are; 1. There is no robust difference in the expression of SARS-CoV-2 entry factors upon particulate exposure, 2. The upstream pathways associated with upregulated genes during SARS-CoV-2 infection considerably overlap with that of PM exposure, 3. Similar pathways were differentially expressed during SARS-CoV-2 infection and PM exposure, 4. SARS-CoV-2 interacting host factors were predicted to be associated with the molecular impact of PM exposure and 5. Differentially expressed pathways during PM exposure may increase COVID-19 severity. Based on the observed molecular mechanisms (direct and indirect effects) the current study suggests that airborne PM exposure has to be considered as an additional co-factor in the outcome of COVID-19.

Exosomal miRNA-19a and miRNA-614 Induced by Air Pollutants Promote Proinflammatory M1 Macrophage Polarization via Regulation of RORα Expression in Human Respiratory Mucosal Microenvironment.

Air pollution exposure leads to various inflammatory diseases in the human respiratory system. Chronic rhinosinusitis is an inflammatory disease caused by viruses, bacteria, or air pollutants. However, the underlying molecular mechanisms through which air particulate matter (PM) causes inflammation and disease remain unclear. In this article, we report that the induction of exosomal microRNAs (miRNAs) from human nasal epithelial cells upon airborne PM exposure promotes proinflammatory M1 macrophage polarization via downregulated RORα expression. Exposure of human nasal epithelial cells to PM results in inflammation-related miRNA expression, and more miRNA is secreted through exosomes delivered to macrophages. Among these, miRNA-19a and miRNA-614 directly bind to the 3'-untranslated region of RORα mRNA and downregulate RORα expression, which leads to inflammation due to inflammatory cytokine upregulation and induces macrophages to a proinflammatory M1-like state. Finally, we showed enhanced expression of miRNA-19a and miRNA-614 but reduced RORα expression in a chronic rhinosinusitis patient tissue compared with the normal. Altogether, our results suggest that PM-induced exosomal miRNAs might play a crucial role in the proinflammatory mucosal microenvironment and macrophage polarization through the regulation of RORα expression.

Folic Acid Supplementation and the Association between Maternal Airborne Particulate Matter Exposure and Preterm Delivery: A National Birth Cohort Study in China.

Background:Potential modification of the association between maternal particulate matter (PM) exposure and preterm delivery (PTD) by folic acid (FA) supplementation has not been studied.Objective:We examined whether FA supplementation could reduce the risk of PTD associated with maternal exposure to PM in ambient air during pregnancy.Method:In a cohort study covering 30 of the 31 provinces of mainland China in 2014, 1,229,556 primiparas of Han ethnicity were followed until labor. We collected information on their FA supplementation and pregnancy outcomes and estimated each participant’s exposure to PM with diameters of (), (), and () using satellite remote-sensing based models. Cox proportional hazard regression models were used to examine interactions between FA supplementation and PM exposures, after controlling for individual characteristics.Results:Participants who initiated FA prior to pregnancy (38.1%) had a 23% [hazard ratio (95% CI: 0.76, 0.78)] lower risk of PTD than women who did not use preconception FA. Participants with PM concentrations in the highest quartile had a higher risk of PTD [ (95% CI: 1.26, 1.32) for , 1.52 (95% CI: 1.46, 1.58) for , and 1.22 (95% CI: 1.17, 1.27) for ] than those with exposures in the lowest PM quartiles. Estimated associations with a increase in and were significantly lower among women who initiated FA prior to pregnancy [ (95% CI: 1.08, 1.10) for both exposures] than among women who did not use preconception FA [ (95% CI: 1.11, 1.13) for both exposures; ]. The corresponding association was also significantly lower for a increase in [ (95% CI: 1.02, 1.03) for FA before pregnancy vs. 1.04 (95% CI: 1.03, 1.04) for no preconception FA; ].Conclusion:Our findings require confirmation in other populations, but they suggest that initiating FA supplementation prior to pregnancy may lessen the risk of PTD associated with PM exposure during pregnancy among primiparas of Han ethnicity. https://doi.org/10.1289/EHP6386

NASA’s Multi-Angle Imager for Aerosols (MAIA): Applications of NASA Satellite Data to Airborne Particulate Matter Exposure and Human Health

The upcoming NASA Multi-Angle Imager for Aerosols (MAIA) investigation seeks to extend NASA’s capabilities to study the impact of different size and compositional mixtures of particulate matter (PM) on adverse health outcomes. The MAIA satellite instrument, in development at the Jet Propulsion Laboratory and planned for launch in mid-2022, will collect multiangular, multispectral, and polarimetric measurements over a set of globally distributed target areas. Retrievals of aerosol properties will be combined with ground-based monitor data and chemical transport modeling to produce 1-km gridded data products of daily-averaged PM10 and PM2.5 mass, as well as the fractional abundances of sulfate, nitrate, organic carbon, elemental carbon, and dust making up the retrieved PM2.5 mixtures. Epidemiologists on the MAIA Science Team and their collaborators will use these data in studies aimed at associating health risk with particle types. The MAIA Early Adopters Program is designed to engage the wider air quality and public health communities and assist them in using MAIA data products, which will be publicly available, free of charge, from NASA’s Atmospheric Science Data Center. This presentation will cover the plans for operational MAIA data products as well as test data products that will be available prior to launch, and opportunities for Early Adopters to become involved in the program.

Combined effects of ambient particulate matter exposure and a high-fat diet on oxidative stress and steatohepatitis in mice.

BackgroundChronic exposure to ambient particulate matter with aerodynamic diameters < 2.5 (PM2.5) induces oxidative injury and liver pathogenesis. The present study assessed the effect and mechanism of long-term, real-world airborne particulate matter (PM) exposure on oxidative stress and hepatic steatosis in the context of a standard chow diet (STD) and a high-fat diet (HFD); the study further explored whether a combination of PM exposure and HFD treatment exacerbates the adverse effects in mice.MethodsC57BL/6J mice fed with STD or HFD (41.26% kcal fat) were exposed to PM or filtered air (FA) for 5 months. Lipid metabolism, oxidative stress and liver pathogenesis were evaluated. Real-time PCR and western blotting were performed to determine gene expression and molecular signal transduction in liver.ResultsChronic airborne PM exposure impaired oxidative homeostasis, caused inflammation and induced hepatic steatosis in mice. Further investigation found that exposure to real-world PM increased the expression of hepatic Nrf2 and Nrf2-regulated antioxidant enzyme gene. The increased protein expression of the sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) in the liver were also observed in PM-exposed groups. Furthermore, the combination of PM exposure and HFD treatment caused a synergistic effect on the changes of lipid accumulation oxidative stress, inflammation in the mouse liver.ConclusionsThrough in vivo study, we reveal that the combination of real-world ambient PM exposure and HFD treatment aggravates hepatic lipid metabolism disorders, inflammation and oxidative stress. PM exposure may accelerate the progression to non-alcoholic steatohepatitis by regulating SREBP-1c/FAS regulatory axis.

Elevated Particulate Matter and Noise Exposure for Spectators at Outdoor Motorsport Events

Since the first recorded steam carriage race in Manchester England, in 1867, motorsport racing has been a globally popular and commercially successful leisure activity. Enthusiasts enjoy a wide range of events, including Formula, stock car, motocross, drag, and many other styles. Despite the many environmental health hazards present at racing events, there have been no published exposure assessment studies for event spectators. To address this knowledge gap, we conducted noise and particulate matter exposure assessment at a series of auto and motocross racing events. Sampling was conducted from May to October, 2017 in designated spectator seating areas at two dirt auto racing tracks, a paved auto racing track, and a dirt motocross track in the St. Louis metro-east region, Illinois, USA, and in Sedalia, Missouri, USA. Using a TSI Instruments SidePak AM520 personal aerosol monitor, arithmetic mean PM2.5 concentration ranged from 51 to 86 µg m-3 across eight race events. Using a Digi-Sense portable sound meter, arithmetic mean noise levels ranged from 75 to 92 dB, and maximum noise levels ranged from 85 to 105 dB across nine race events. PM2.5 at individual race events was combined with 24 hr average concentration data from Illinois EPA&amp;#8217;s Granite City, IL ambient air monitoring sites to obtain time weighted average estimated 24 hour PM2.5 exposure for race spectators. Based on these calculations, 24 hour PM2.5 for race spectators would be 1.8 to 3.5 times local background exposure. These values corresponded to EPA Air Quality Index levels of 63 to 92, falling in the Moderate category, which presents potential respiratory symptoms to highly sensitive individuals. Planned future data collection includes gravimetric sampling, and particle composition analyses. Our results suggest that despite the short duration of these activities, there are possible respiratory hazards from airborne particulate matter exposure for spectators with preexisting vulnerability.

Combination effects of airborne particulate matter exposure and high-fat diet on hepatic fibrosis through regulating the ROS-endoplasmic reticulum stress-TGFβ/SMADs axis in mice

BackgroundHepatic fibrosis, characterized by an excessive accumulation of extracellular matrix, is associated with toxic substance exposure, chronic infections, mechanical injury, airborne fine particulate matter (PM2.5) exposure and metabolic disease. This study aimed to investigate the effect and mechanism of long-term, real-world airborne particulate matter (PM) exposure on hepatic fibrosis and further explored whether combination treatment of PM exposure and high-fat diet (HFD) aggravate the adverse effects in mice. Methods and resultsSix-week-old male C57BL/6J mice fed with either a standard chow diet (STD) or an HFD were treated with either filtered air (FA) or PM for 18 weeks. Metabolic parameters, histological examination, gene expression analysis, and Western blot analysis were utilized to measure the effect and mechanism of PM exposure on hepatic fibrosis and to further analyze the synergistic effect of HFD. Subchronic airborne PM exposure induces hepatic fibrosis in mice, and combination treatment of PM exposure and HFD accelerate the adverse effect. Meanwhile, subchronic exposure to real-world PM increased the level of hepatic ROS, and the expression of endoplasmic reticulum (ER) stress markers (GRP78 and CHOP), p-SMAD2 and p-SMAD3, as well as up-regulated TGFβ and collagen 1 in liver tissues. Furthermore, PM exposure and HFD displayed the synergistic effects on these changes in liver. ConclusionOur findings indicate that airborne PM exposure aggravates HFD -induced hepatic fibrosis. The ROS-ER stress-TGFβ/SMADs regulatory axis mediates the effects of airborne PM exposure on accelerating hepatic fibrosis.

Airborne Particulate Matter Induces Nonallergic Eosinophilic Sinonasal Inflammation in Mice

Exposure to airborne particulate matter (PM) has been linked to aggravation of respiratory symptoms, increased risk of cardiovascular disease, and all-cause mortality. Although the health effects of PM on the lower pulmonary airway have been extensively studied, little is known regarding the impact of chronic PM exposure on the upper sinonasal airway. We sought to test the impact of chronic airborne PM exposure on the upper respiratory system in vivo. Mice were subjected, by inhalation, to concentrated fine (2.5 μm) PM 6 h/d, 5 d/wk, for 16 weeks. Mean airborne fine PM concentration was 60.92 μm/m3, a concentration of fine PM lower than that reported in some major global cities. Mice were then killed and analyzed for evidence of inflammation and barrier breakdown compared with control mice. Evidence of the destructive effects of chronic airborne PM on sinonasal health in vivo, including proinflammatory cytokine release, and macrophage and neutrophil inflammatory cell accumulation was observed. A significant increase in epithelial barrier dysfunction was observed, as assessed by serum albumin accumulation in nasal airway lavage fluid, as well as decreased expression of adhesion molecules, including claudin-1 and epithelial cadherin. A significant increase in eosinophilic inflammation, including increased IL-13, eotaxin-1, and eosinophil accumulation, was also observed. Collectively, although largely observational, these studies demonstrate the destructive effects of chronic airborne PM exposure on the sinonasal airway barrier disruption and nonallergic eosinophilic inflammation in mice.