Primary and secondary transcriptional effects of traffic-related air pollution in human lung and coronary artery cells

Air pollution induces adverse respiratory and cardiovascular effects, yet the intitial mechanisms driving the exposure-outcome pathways remain unclear. Fully differentiated primary human bronchical epithelial (NHBE) cells were exposed to aerosol diesel exhaust (DE) at 300 µg/m3 or filtered air (FA) for 1 hour in an electrostatic particle deposition chamber (NACIVT) under physiological conditions. We used freshly generated, aged, diluted DE as a model for urban air polltion. Following exposure, cells were incubated for 3 or 24 hours. To investigate secondary effects of circulating mediators released by the lung, we exposed primary human coronary artery endothelial cells (HCAEC) to conditioned media from the NHBE studies for 4 hours. mRNA samples were multiplexed using the Fluidigm-based qPCR assay for genes related to inflammation, oxidative stress and barrier function. Compared with FA, DE exposed NHBE cells showed significant upregulation in the expressin of 9 genes (GCLc, HIF1α, ICAM1, COX2, ZO-1, MMP2, IL-6, CCL2, and SLPI, all FDR Our data reveal transcriptional changes in primary human cells that may underlie early pathophysiological effects of inhaled pollutants. More importantly, we provide evidence that pollutant effects intiated in the airway epithelium can induce secondary effects in coronary artery cells, suggesting that the epithelium plays an initial role in inflammatory processes and barrier dysfunction outside of the lung.