Identification of a Common Gene Expression Response in Different Lung Inflammatory Diseases in Rodents and Macaques

To identify gene expression responses common to multiple pulmonary diseases we collected microarray data for acute lung inflammation models from 12 studies and used these in a meta-analysis. The data used include exposures to air pollutants; bacterial, viral, and parasitic infections; and allergic asthma models. Hierarchical clustering revealed a cluster of 383 up-regulated genes with a common response. This cluster contained five subsets, each characterized by more specific functions such as inflammatory response, interferon-induced genes, immune signaling, or cell proliferation. Of these subsets, the inflammatory response was common to all models, interferon-induced responses were more pronounced in bacterial and viral models, and a cell division response was more prominent in parasitic and allergic models. A common cluster containing 157 moderately down-regulated genes was associated with the effects of tissue damage. Responses to influenza in macaques were weaker than in mice, reflecting differences in the degree of lung inflammation and/or virus replication. The existence of a common cluster shows that in vivo lung inflammation in response to various pathogens or exposures proceeds through shared molecular mechanisms

Inhalable Textile Microplastic Fibers Impair Airway Epithelial Differentiation

Rationale: Microplastics are a pressing global concern and inhalation of microplastic fibers has been associated with interstitial and bronchial inflammation in flock workers. However, how microplastic fibers affect the lungs is unknown. Objectives: Our aim was to assess the effects of 12x31 µm nylon 6,6 (nylon) and 15x52 µm polyethylene terephthalate (polyester) textile microplastic fibers on lung epithelial growth and differentiation. Methods: We used human and murine alveolar and airway-type organoids as well as air-liquid interface cultures derived from primary lung epithelial progenitor cells and incubated these with either nylon or polyester fibers or nylon leachate. In addition, mice received one dose of nylon fibers or nylon leachate and 7 days later organoid-forming capacity of isolated epithelial cells was investigated. Measurements and Main Results: We observed that nylon microfibers, more than polyester, inhibited developing airway organoids and not established ones. This effect was mediated by components leaching from nylon. Epithelial cells isolated from mice exposed to nylon fibers or leachate, also formed fewer airway organoids, suggesting long-lasting effects of nylon components on epithelial cells. Part of these effects were recapitulated in human air-liquid interface cultures. Transcriptome analysis revealed upregulation of Hoxa5 post-exposure to nylon fibers. Inhibiting Hoxa5 during nylon exposure restored airway organoid formation, confirming Hoxa5's pivotal role in the effects of nylon. Conclusions: These results suggest that components leaching from nylon 6,6 may especially harm developing airways and/or airways undergoing repair and we strongly encourage to characterize both hazard of and exposure to microplastic fibers in more detail

The relationship of air pollution and surrogate markers of endothelial dysfunction in a population-based sample of children

<p>Abstract</p> <p>Background</p> <p>This study aimed to assess the relationship of air pollution and plasma surrogate markers of endothelial dysfunction in the pediatric age group.</p> <p>Methods</p> <p>This cross-sectional study was conducted in 2009-2010 among 125 participants aged 10-18 years. They were randomly selected from different areas of Isfahan city, the second large and air-polluted city in Iran. The association of air pollutants' levels with serum thrombomodulin (TM) and tissue factor (TF) was determined after adjustment for age, gender, anthropometric measures, dietary and physical activity habits.</p> <p>Results</p> <p>Data of 118 participants was complete and was analyzed. The mean age was 12.79 (2.35) years. The mean pollution standards index (PSI) value was at moderate level, the mean particular matter measuring up to 10 μm (PM₁₀) was more than twice the normal level. Multiple linear regression analysis showed that TF had significant relationship with all air pollutants except than carbon monoxide, and TM had significant inverse relationship with ozone. The odds ratio of elevated TF was significantly higher in the upper vs. the lowest quartiles of PM₁₀, ozone and PSI. The corresponding figures were in opposite direction for TM.</p> <p>Conclusions</p> <p>The relationship of air pollutants with endothelial dysfunction and pro-coagulant state can be an important factor in the development of atherosclerosis from early life. This finding should be confirmed in future longitudinal studies. Concerns about the harmful effects of air pollution on children's health should be considered a top priority for public health policy; it should be underscored in primordial and primary prevention of chronic diseases.</p

Inventarisatie van biomarkers voor oxidatieve stress

This inventory was carried out under the project 'Reducing uncertainties in the causality between inhalation exposure and health' prepared in the framework of strategic research at the National Institute for Public Health and the Environment (RIVM). The aim of the project is to validate a model to reduce uncertainties in the causality between inhalation exposure and health effects. The underlying question here is whether health effects due to air pollution are facilitated by an oxidative stress mechanism. This biomarker inventory for oxidative stress is one of the products resulting from this project. Oxidative stress results either due to increased exposure to reactive oxygen species or to the presence of decreased antioxidant defences, resulting in damage to macromolecules. Biomarkers that could be of interest for studying the role of oxidative stress in air pollution-related health effects are carbonyl levels as a measure for oxidized proteins, thiobarbituric acid-reactive substances for total lipid oxidation and 8-hydroxy-deoxyguanosine for oxidative injury to DNA. In the antioxidant response, superoxide dismutase, heme oxygenase, metallothioneins, and thioredoxin reductase and glutathion could be valuable markers.Deze inventarisatie is geschreven als product van het project 'Vermindering van onzekerheden in causale relaties tussen inhalatoire blootstelling en gezondheidseffecten', welke wordt uitgevoerd in het kader van het strategisch onderzoek Rijksinstituut voor Volksgezondheid en Milieu (RIVM). Dit project richt zich op reductie van onzekerheden in de causale relaties tussen inhalatoire blootstelling en gezondheidseffecten met behulp van dierexperimenteel onderzoek. De onderliggende vraag hierbij is of de gezondheidseffecten ten gevolge van luchtverontreiniging veroorzaakt worden door oxidatieve stress.Oxidatieve stress kan enerzijds ontstaan door verhoogde blootstelling aan reactieve zuurstofdeeltjes of anderzijds door verlaging van antioxidantia. In beide gevallen kan dit resulteren in schade aan macromoleculen (eiwitten, lipiden en DNA). Biomarkers voor oxidatieve stress welke binnen het project van belang kunnen zijn, zijn: carbonyl niveaus als maat voor geoxideerde eiwitten, 'thiobarbituric acid-reactive substances' als maat voor lipide oxidatie en 8-hydroxy-deoxyguanosine als maat voor oxidatieve schade aan DNA. In de antioxidant respons kunnen, superoxide dismutase, heemoxygenase, metallothioneins, thioredoxine reductase en glutathion als waardevolle markers fungeren

Inventarisatie van biomarkers voor oxidatieve stress

Deze inventarisatie is geschreven als product van het project 'Vermindering van onzekerheden in causale relaties tussen inhalatoire blootstelling en gezondheidseffecten', welke wordt uitgevoerd in het kader van het strategisch onderzoek Rijksinstituut voor Volksgezondheid en Milieu (RIVM). Dit project richt zich op reductie van onzekerheden in de causale relaties tussen inhalatoire blootstelling en gezondheidseffecten met behulp van dierexperimenteel onderzoek. De onderliggende vraag hierbij is of de gezondheidseffecten ten gevolge van luchtverontreiniging veroorzaakt worden door oxidatieve stress.Oxidatieve stress kan enerzijds ontstaan door verhoogde blootstelling aan reactieve zuurstofdeeltjes of anderzijds door verlaging van antioxidantia. In beide gevallen kan dit resulteren in schade aan macromoleculen (eiwitten, lipiden en DNA). Biomarkers voor oxidatieve stress welke binnen het project van belang kunnen zijn, zijn: carbonyl niveaus als maat voor geoxideerde eiwitten, 'thiobarbituric acid-reactive substances' als maat voor lipide oxidatie en 8-hydroxy-deoxyguanosine als maat voor oxidatieve schade aan DNA. In de antioxidant respons kunnen, superoxide dismutase, heemoxygenase, metallothioneins, thioredoxine reductase en glutathion als waardevolle markers fungeren.This inventory was carried out under the project 'Reducing uncertainties in the causality between inhalation exposure and health' prepared in the framework of strategic research at the National Institute for Public Health and the Environment (RIVM). The aim of the project is to validate a model to reduce uncertainties in the causality between inhalation exposure and health effects. The underlying question here is whether health effects due to air pollution are facilitated by an oxidative stress mechanism. This biomarker inventory for oxidative stress is one of the products resulting from this project. Oxidative stress results either due to increased exposure to reactive oxygen species or to the presence of decreased antioxidant defences, resulting in damage to macromolecules. Biomarkers that could be of interest for studying the role of oxidative stress in air pollution-related health effects are carbonyl levels as a measure for oxidized proteins, thiobarbituric acid-reactive substances for total lipid oxidation and 8-hydroxy-deoxyguanosine for oxidative injury to DNA. In the antioxidant response, superoxide dismutase, heme oxygenase, metallothioneins, and thioredoxin reductase and glutathion could be valuable markers.DG RIV