Gene expression profiling of human bronchial epithelial cells exposed to fine particulate matter (PM2.5) from biomass combustion

摘要

One-third of the world's population relies on solid biomass fuels for domestic energy demands. In contrast to industrial or traffic related emissions, only a limited number of studies focus on the adverse health effects of particulate matter (PM) from biomass combustion. We conducted Affymetrix Human Genome U133 Plus 2.0 arrays, bioinformatic analysis, qRT-PCR and immunoblotting to determine the molecular impact of fuelwood-derived PM2.5 on lung epithelial BEAS-2B cells. In the presence of PM2.5 175 differentially regulated genes were identified. Gene ontology (GO), pathway and functional enrichment analysis allocated these genes to cellular development, metabolism, inflammation, cancer and the immune system. Analysis of enriched transcription factor binding sites extracted 15 PM2.5 responsive transcription factors, including the polycyclic aromatic hydrocarbon (PAH)-activated aryl hydrocarbon receptor (AhR). Accordingly, a complex mixture of PAHs was detected in the PM2.5 fraction using APLI and AhR-inhibitors reduced the up-regulation of CYP1A1, EREG, GREM1, IL1B and IL6, indicating that PAHs are involved in PM2.5 specific gene deregulation. We also provide evidence, that HIF-1 alpha might be responsive to PM2.5. To analyze the impact of microbial infections, PM2.5 predisposed cells were incubated with LPS or dsRNA. We identified 40 LPS and 380 dsRNA specific genes in PM2.5 predisposed cells. GO allocated these genes with chemokine dependent and inflammatory pathways, viral responses and xenobiotic metabolism. A disease ontology allocated lung and lung associated diseases to PM2.5 exposed cells. In some cases LPS or dsRNA increased significance of probability of diseases. Altogether our studies enhance our knowledge on the mechanism promoting harmful effects of PM.