Expression profiling by high throughput sequencing
Summary
Exposure to ambient particulate matter (PM) is associated with adverse health effects. Yet, due to the complexity of its chemical composition, the molecular effects of PM exposure and the mechanism of PM-mediated toxicity remain largely unknown. Here, we show that water-soluble inorganics such as nitrate and sulfate ions, rather than PM themselves, are responsible for perturbing gene expression in the lungs by rapidly penetrating the lung surfactant barrier to the alveolar region. Furthermore, from high-throughput sequencing of lung adenocarcinoma cells, we find that exposure to nitrate and sulfate ions activates the cholesterol biosynthetic metabolism and induces the expression of genes related to tumorigenesis and inflammatory response, particularly interferon-gamma. Transcriptome analysis of mouse lungs exposed to nitrate/sulfate aerosols further supports our findings. Notably, we find that exposure to nitrate/sulfate mixture leads to a unique gene expression pattern that is not observed when nitrate or sulfate is treated alone. Our work suggests the water-soluble ions as a potential source of PM-mediated toxicity and provides a roadmap to unveil the working mechanism of health hazards of PM exposure.
Overall design
mRNA-sequencing was performed in A549 cells or mouse lung tissue under ammonium nitrate or sulfate treatment. Two replicates were used for each sample
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