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

Popadic D, Heßelbach K, Richter-Brockmann S, Kim G-J, Flemming S, Schmidt-Heck W, Häupl T, Bonin M, Dornhof R, Achten C, Günther S, Humar M, Merfort I

Abstract

One-third of the world's population relies on solid biomass fuels for domestic energy demands. In contrast toindustrial or traffic related emissions, only a limited number of studies focus on the adverse health effects ofparticulate matter (PM) from biomass combustion. We conducted Affymetrix Human Genome U133 Plus 2.0arrays, bioinformatic analysis, qRT-PCR and immunoblotting to determine the molecular impact of fuelwoodderivedPM2.5 on lung epithelial BEAS-2B cells. In the presence of PM2.5 175 differentially regulated genes wereidentified. Gene ontology (GO), pathway and functional enrichment analysis allocated these genes to cellulardevelopment, metabolism, inflammation, cancer and the immune system. Analysis of enriched transcriptionfactor 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 wasdetected 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 provideevidence, that HIF-1α might be responsive to PM2.5. To analyze the impact of microbial infections, PM2.5 predisposedcells were incubated with LPS or dsRNA. We identified 40 LPS and 380 dsRNA specific genes in PM2.5predisposed cells. GO allocated these genes with chemokine dependent and inflammatory pathways, viral responsesand xenobiotic metabolism. A disease ontology allocated lung and lung associated diseases to PM2.5exposed cells. In some cases LPS or dsRNA increased significance of probability of diseases. Altogether ourstudies enhance our knowledge on the mechanism promoting harmful effects of PM.