Lung Inflammatory Response to Environmental Dust Exposure in Mice Suggests a Link to Regional Respiratory Disease Risk.

PURPOSE: The Salton Sea, California's largest lake, is designated as an agricultural drainage reservoir. In recent years, the lake has experienced shrinkage due to reduced water sources, increasing levels of aerosolized dusts in surrounding regions. Communities surrounding the Salton Sea have increased asthma prevalence versus the rest of California; however, a connection between dust inhalation and lung health impacts has not been defined. METHODS: We used an established intranasal dust exposure murine model to study the lung inflammatory response following single or repetitive (7-day) exposure to extracts of dusts collected in regions surrounding the Salton Sea (SSDE), complemented with in vitro investigations assessing SSDE impacts on the airway epithelium. RESULTS: In these investigations, single or repetitive SSDE exposure induced significant lung inflammatory cytokine release concomitant with neutrophil influx. Repetitive SSDE exposure led to significant lung eosinophil recruitment and altered expression of genes associated with allergen-mediated immune response, including Clec4e. SSDE treatment of human bronchial epithelial cells (BEAS-2B) induced inflammatory cytokine production at 5- and 24-hours post-treatment. When BEAS-2B were exposed to protease activity-depleted SSDE (PDSSDE) or treated with SSDE in the context of protease-activated receptor-1 and -2 antagonism, inflammatory cytokine release was decreased. Furthermore, repetitive exposure to PDSSDE led to decreased neutrophil and eosinophilic influx and IL-6 release in mice compared to SSDE-challenged mice. CONCLUSION: These investigations demonstrate potent lung inflammatory responses and tissue remodeling in response to SSDE, in part due to environmental proteases found within the dusts. These studies provide the first evidence supporting a link between environmental dust exposure, protease-mediated immune activation, and respiratory disease in the Salton Sea region.

Integrative Analysis of lncRNA-mRNA Coexpression in Human Lung Epithelial Cells Exposed to Dimethyl Selenide-Derived Secondary Organic Aerosols.

Dimethyl selenide (DMSe) is one of the major volatile organoselenium compounds released into the atmosphere through plant metabolism and microbial methylation. DMSe has been recently revealed as a precursor of secondary organic aerosol (SOA), and its resultant SOA possesses strong oxidizing capability toward thiol groups that can perturb several major biological pathways in human airway epithelial cells and is linked to genotoxicity, DNA damage, and p53-mediated stress responses. Mounting evidence has suggested that long noncoding RNAs (lncRNAs) are involved in stress responses to internal and environmental stimuli. However, the underlying molecular interactions remain to be elucidated. In this study, we performed integrative analyses of lncRNA-mRNA coexpression in the transformed human bronchial epithelial BEAS-2B cell line exposed to DMSe-derived SOA. We identified a total of 971 differentially expressed lncRNAs in BEAS-2B cells exposed to SOA derived from O3 and OH oxidation of DMSe. Gene ontology (GO) network analysis of cis-targeted genes showed significant enrichment of DNA damage, apoptosis, and p53-mediated stress response pathways. trans-Acting lncRNAs, including PINCR, PICART1, DLGAP1-AS2, and LINC01629, known to be associated with human carcinogenesis, also showed altered expression in cell treated with DMSe-SOA. Overall, this study highlights the regulatory role of lncRNAs in altered gene expression induced by DMSe-SOA exposure.

Exposure to Dimethyl Selenide (DMSe)-Derived Secondary Organic Aerosol Alters Transcriptomic Profiles in Human Airway Epithelial Cells.

Dimethyl selenide (DMSe) is one of the major volatile organoselenium compounds released from aquatic and terrestrial environments through microbial transformation and plant metabolism. The detailed processes of DMSe leading to secondary organic aerosol (SOA) formation and the pulmonary health effects induced by inhalation of DMSe-derived SOA remain largely unknown. In this study, we characterized the chemical composition and formation yields of SOA produced from the oxidation of DMSe with OH radicals and O3 in controlled chamber experiments. Further, we profiled the transcriptome-wide gene expression changes in human airway epithelial cells (BEAS-2B) after exposure to DMSe-derived SOA. Our analyses indicated a significantly higher SOA yield resulting from the OH-initiated oxidation of DMSe. The oxidative potential of DMSe-derived SOA, as measured by the dithiothreitol (DTT) assay, suggested the presence of oxidizing moieties in DMSe-derived SOA at levels higher than typical ambient aerosols. Utilizing RNA sequencing (RNA-Seq) techniques, gene expression profiling followed by pathway enrichment analysis revealed several major biological pathways perturbed by DMSe-derived SOA, including elevated genotoxicity, DNA damage, and p53-mediated stress responses, as well as downregulated cholesterol biosynthesis, glycolysis, and interleukin IL-4/IL-13 signaling. This study highlights the significance of DMSe-derived SOA as a stressor in human airway epithelial cells.