Dataset Information

Human airway construct model is suitable for studying transcriptome changes associated with indoor air particulate matter toxicity.

ABSTRACT: In vitro models mimicking the human respiratory system are essential when investigating the toxicological effects of inhaled indoor air particulate matter (PM). We present a pulmonary cell culture model for studying indoor air PM toxicity. We exposed normal human bronchial epithelial cells, grown on semi-permeable cell culture membranes, to four doses of indoor air PM in the air-liquid interface. We analyzed the chemokine interleukin-8 concentration from the cell culture medium, protein concentration from the apical wash, measured tissue electrical resistance, and imaged airway constructs using light and transmission electron microscopy. We sequenced RNA using a targeted RNA toxicology panel for 386 genes associated with toxicological responses. PM was collected from a non-complaint residential environment over 1 week. Sample collection was concomitant with monitoring size-segregated PM counts and determination of microbial levels and diversity. PM exposure was not acutely toxic for the cells, and we observed up-regulation of 34 genes and down-regulation of 17 genes when compared to blank sampler control exposure. The five most up-regulated genes were related to immunotoxicity. Despite indications of incomplete cell differentiation, this model enabled the comparison of a toxicological transcriptome associated with indoor air PM exposure.

SUBMITTER: Nordberg ME

PROVIDER: S-EPMC7217003 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Human airway construct model is suitable for studying transcriptome changes associated with indoor air particulate matter toxicity.

Nordberg Maria-Elisa ME Täubel Martin M Jalava Pasi I PI BéruBé Kelly K Tervahauta Arja A Hyvärinen Anne A Huttunen Kati K

Indoor air 20200123 3

In vitro models mimicking the human respiratory system are essential when investigating the toxicological effects of inhaled indoor air particulate matter (PM). We present a pulmonary cell culture model for studying indoor air PM toxicity. We exposed normal human bronchial epithelial cells, grown on semi-permeable cell culture membranes, to four doses of indoor air PM in the air-liquid interface. We analyzed the chemokine interleukin-8 concentration from the cell culture medium, protein concentr ...[more]

PMID: 31883508

Similar Datasets

Project description:Background - Multiple health effects are associated with moisture damage in buildings. Studies explaining these associations and cell-level mechanisms behind the observed health effects are urgently called for. Objectives - Alongside general toxicological markers, we focused on characterizing gene expression in human airway epithelium after exposure to indoor air particulate matter (PM) sampled from houses with and without moisture damage. Methods - We performed detailed technical building inspections in 25 residential houses and categorized them based on the detection of moisture damages and the probability of occupant exposure. PM sampling was complemented by microbiological and volatile organic compound assessment. We exposed airway constructs to three doses (1:16, 1:8, 1:4) of PM from moisture-damaged (index) and non-moisture-damaged (reference) houses. The RNA of exposed constructs was sequenced targeting toxicology -related genes. We did groupwise comparisons between index and reference houses and pairwise comparisons in matched index/reference houses. We analyzed general toxicological markers and imaged the constructs with electron microscopy. Results - In pairwise comparison, several genes were differentially expressed. Genes related to multiple toxicological pathways were highlighted, while none of the genes was consistently expressed in all the comparisons. In groupwise comparison, CYP1A1 was statistically significantly over-expressed in index houses at all doses (dose 1:16 log2FC = 0.007, padj = 0.03; dose 1:8 log2FC = 0.077, padj = 0.018; dose 1:4 log2FC = 0.270, padj = 0.002) and NFKB1 at the highest dose 1:4 (log2FC = 0.124, padj = 0.029). General toxicological markers did not separate the index/reference houses. Discussion - The exposure to PM from index houses activates toxicology -related genes in airway constructs. While differential expression was not consistent among all the index/reference pairs, possibly due to compositional differences of bioactive particles, our study highlights CYP1A1 and NFKB1 as potential targets in moisture damage -associated cellular responses.

Project description:People generally spend more time indoors than outdoors resulting in a higher proportion of exposure to particulate matter (PM) occurring indoors. Consequently, indoor PM levels, in contrast to outdoor PM levels, may have a stronger relationship with lung function. To test this hypothesis, indoor and outdoor PM2.5 and fungal spore data were simultaneously collected from the homes of forty-four asthmatic children aged 10-16?years. An optical absorption technique was utilized on the collected PM2.5 mass to obtain concentrations of black carbon (BC) and ultraviolet light absorbing particulate matter, (UVPM; a marker of light absorbing PM2.5 emitted from smoldering organics). Enrolled children completed spirometry after environmental measurements were made. Given the high correlation between PM2.5, BC, and UVPM, principal component analysis was used to obtain uncorrelated summaries of the measured PM. Separate linear mixed-effect models were developed to estimate the association between principal components of the PM variables and spirometry values, as well as the uncorrelated original PM variables and spirometry values. A one-unit increase in the first principal component variable representing indoor PM (predominantly composed of UVPM and PM2.5) was associated with 4.1% decrease (99% CI?=?-6.9, -1.4) in FEV1/FVC ratio. 11.3??g/m3 increase in indoor UVPM was associated with 6.4% and 14.7% decrease (99% CI?=?-10.4, -2.4 and 99% CI?=?-26.3, -2.9, respectively) in percent predicted FEV1/FVC ratio and FEF25-75 respectively. Additionally, 17.7??g/m3 increase in indoor PM2.5 was associated with 6.1% and 12.9% decrease (99% CI?=?-10.2, -1.9 and 99% CI?=?-24.9, -1.0, respectively) in percent predicted FEV1/FVC ratio and FEF25-75, respectively. Outdoor PM, indoor BC, and indoor fungal spores were not significantly associated with lung function. The results indicate that indoor PM is more strongly associated with lung function in children with asthma as compared with outdoor PM.

Project description:Background: Particulate matter (PM) air pollution causes deleterious health effects; however, less is known about health effects of indoor air particulate matter (IAP). Objective: To understand whether IAP influences distinct mechanisms in the development of respiratory tract infections, including bacterial growth, biofilm formation, and innate immunity. Additionally, we tested whether IAP from Iowa houses of subjects with and without recent respiratory exacerbations recapitulated the National Institute of Standards and Technology (NIST) IAP findings. Methods: To test the effect of NIST and Iowa IAP on bacterial growth and biofilm formation, we assessed Staphylococcus aureus growth and Pseudomonas aeruginosa biofilm formation with and without the presence of IAP. To assess the effect of IAP on innate immunity, we exposed primary human airway surface liquid (ASL) to NIST, and Iowa IAP. Lastly, we tested whether specific metals may be responsible for effects on airway innate immunity. Results: NIST and Iowa IAP significantly enhanced bacterial growth and biofilm formation. NIST IAP (whole particle and the soluble portion) impaired ASL antimicrobial activity. IAP from one Iowa home significantly impaired ASL antimicrobial activity (p < 0.05), and five other homes demonstrated a trend (p ≤ 0.18) of impaired ASL antimicrobial activity. IAP from homes of subjects with a recent history of respiratory exacerbation tended (p = 0.09) to impair ASL antimicrobial activity more than IAP from homes of those without a history respiratory exacerbation. Aluminum and Magnesium impaired ASL antimicrobial activity, while copper was bactericidal. Combining metals varied their effect on ASL antimicrobial activity. Conclusions: NIST IAP and Iowa IAP enhanced bacterial growth and biofilm formation. ASL antimicrobial activity was impaired by NIST IAP, and Iowa house IAP from subjects with recent respiratory exacerbation tended to impair ASL antimicrobial activity. Individual metals may explain impaired ASL antimicrobial activity; however, antimicrobial activity in the presence of multiple metals warrants further study.

Project description:Autism is a heterogeneous disorder with genetic and environmental factors likely contributing to its origins. Examination of hazardous pollutants has suggested the importance of air toxics in the etiology of autism, yet little research has examined its association with local levels of air pollution using residence-specific exposure assignments.To examine the relationship between traffic-related air pollution, air quality, and autism.This population-based case-control study includes data obtained from children with autism and control children with typical development who were enrolled in the Childhood Autism Risks from Genetics and the Environment study in California. The mother's address from the birth certificate and addresses reported from a residential history questionnaire were used to estimate exposure for each trimester of pregnancy and first year of life. Traffic-related air pollution was assigned to each location using a line-source air-quality dispersion model. Regional air pollutant measures were based on the Environmental Protection Agency's Air Quality System data. Logistic regression models compared estimated and measured pollutant levels for children with autism and for control children with typical development.Case-control study from California.A total of 279 children with autism and a total of 245 control children with typical development.Crude and multivariable adjusted odds ratios (AORs) for autism.Children with autism were more likely to live at residences that had the highest quartile of exposure to traffic-related air pollution, during gestation (AOR, 1.98 [95% CI, 1.20-3.31]) and during the first year of life (AOR, 3.10 [95% CI, 1.76-5.57]), compared with control children. Regional exposure measures of nitrogen dioxide and particulate matter less than 2.5 and 10 ?m in diameter (PM2.5 and PM10) were also associated with autism during gestation (exposure to nitrogen dioxide: AOR, 1.81 [95% CI, 1.37-3.09]; exposure to PM2.5: AOR, 2.08 [95% CI, 1.93-2.25]; exposure to PM10: AOR, 2.17 [95% CI, 1.49-3.16) and during the first year of life (exposure to nitrogen dioxide: AOR, 2.06 [95% CI, 1.37-3.09]; exposure to PM2.5: AOR, 2.12 [95% CI, 1.45-3.10]; exposure to PM10: AOR, 2.14 [95% CI, 1.46-3.12]). All regional pollutant estimates were scaled to twice the standard deviation of the distribution for all pregnancy estimates.Exposure to traffic-related air pollution, nitrogen dioxide, PM2.5, and PM10 during pregnancy and during the first year of life was associated with autism. Further epidemiological and toxicological examinations of likely biological pathways will help determine whether these associations are causal.

Dataset Information

Human airway construct model is suitable for studying transcriptome changes associated with indoor air particulate matter toxicity.

Publications

Human airway construct model is suitable for studying transcriptome changes associated with indoor air particulate matter toxicity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure