Human airway construct model is suitable for studying transcriptome changes associated with indoor air particulate matter toxicity

Abstract

In vitro models mimicking the human respiratory system are essential when investigating the toxicological effects of inhaled indoor air particulate matter (PM). We present a pulmonary cell culture model for studying indoor air PM toxicity. We exposed normal human bronchial epithelial cells, grown on semi‐permeable cell culture membranes, to four doses of indoor air PM in the air‐liquid interface. We analyzed the chemokine interleukin‐8 concentration from the cell culture medium, protein concentration from the apical wash, measured tissue electrical resistance, and imaged airway constructs using light and transmission electron microscopy. We sequenced RNA using a targeted RNA toxicology panel for 386 genes associated with toxicological responses. PM was collected from a non‐complaint residential environment over 1 week. Sample collection was concomitant with monitoring size‐segregated PM counts and determination of microbial levels and diversity. PM exposure was not acutely toxic for the cells, and we observed up‐regulation of 34 genes and down‐regulation of 17 genes when compared to blank sampler control exposure. The five most up‐regulated genes were related to immunotoxicity. Despite indications of incomplete cell differentiation, this model enabled the comparison of a toxicological transcriptome associated with indoor air PM exposure