Perfluorohexanoic acid (PFHxA) induces cytochrome P450 expression and enzymatic activity in well-differentiated primary human bronchial epithelial (HBE) cells

Perfluorohexanoic acid (PFHxA) is a short-chain perfluoroalkyl substance (PFAS) used as a substitute for perfluorooctanoic acid (PFOA) and occurs as a degradation product from long-chain PFAS. PFHxA is found in consumer products and increasingly detected as an indoor dust contaminant suggesting the lung as the target of inhaled PFHxA exposure. Therefore, we aimed to identify potential adverse impacts of PFHxA on primary human bronchial epithelial (HBE) cells, differentiated from basal stem cells in a three-dimensional air-liquid interface culture. This culture forms a pseudostratified epithelium that recapitulates the cellular composition and barrier function of the airway. Using this gold-standard in vitro model of airway cell biology, we performed dose- and time-dependent experiments. Our results indicate that PFHxA exposure up to 1000 nM neither decreases cell viability nor adversely affects epithelial barrier function in HBE cells. However, exposure to 1000 nM PFHxA for 72 h reduced the number of ciliated cells in two donors. Additionally, induction of cytochrome P450 (CYP450) was observed at 24, 48, and 72 h of PFHxA exposure, indicated by increased CYP1A1 and CYP1B1 mRNA expression, CYP1B1 protein expression, and CYP450 enzyme activity. These findings underscore the need for further investigation into PFHxA exposure and its effects on lung health. • Human bronchial epithelial cells were exposed to perfluorohexanoic acid (PFHxA). • PFHxA did not adversely affect epithelial barrier function or cell viability. • Exposure to 1000 nM PFHxA for 72 h decreased the number of ciliated cells. • PFHxA induced CYP450 expression and activity after 24, 48, and 72 h of exposure.