Transcriptional modulation of a human monocytic cell line exposed to PM10 from an urban area

Insight into the mechanisms by which ambient air particulate matter mediates adverse health effects is needed to provide biological plausibility to epidemiological studies demonstrating an association between PM10 exposure and increased morbidity and mortality. In vitro studies of the effects of air pollution on human cells help to establish conditions for the analysis of cause–effect relationships. One of the major challenges is to test native atmosphere in its complexity, rather than the various components individually. We have developed an in vitro system in which human monocyte-macrophage U937 cells are directly exposed to filters containing different amounts of PM10 collected in the city of Rome.Transcriptional profiling obtained after short exposure (1 h) of cells to a filter containing 1666 μg PM10 (77.6 μg/cm2) using a macroarray panel of 1176 genes reveals a significant change in the mRNA level (>2 fold) for 87 genes relative to cells exposed to a control filter. Overall, 9 out of 87 modulated genes were annotated as “lung cancer”. qRT-PCR confirmed the induction of relevant genes involved in DNA repair and apoptosis, specifically: ERCC1, TDG, DAD1 and MCL1. In cells exposed for 10 min, 1 h and 3 h to different amounts of PM10, transcription of TNFα and TRAP1, which code for a key pro-inflammatory cytokine and a mitochondrial protein involved in cell protection from oxidative stress, respectively, was shown to be modulated in a time-dependent, but not a dose-dependent manner.Taken together, these data indicate that it is possible to analyze the effects of untreated particulate matter on human cells by the direct-exposure approach we have developed, possibly providing new clues to traffic-related health hazard.

► DNA repair ERCC1 and TDG genes are up-regulated by ambient PM10 in human cells.
► Oxidative stress induced by PM10 modulates TNFα and TRAP1 gene expression.
► PM10 effects depend on the specific composition rather than on the exact amount.