Regional and size-dependent effects of ambient agricultural particulate matter on Ah-receptor activity and inflammatory responses in human U937 macrophages

AIMS: Size-fractionated ambient particulate matter (PM) was collected from two of the most highly PM-polluted agricultural regions in California the Imperial Valley (PMIV), and San Joaquin Valley (Parlier, PMPA), to compare the effects of particle source, size, and duration of exposure on inflammatory gene expression, cell viability, and aryl hydrocarbon receptor (AhR) activation. METHODS: Here we tested that the chemical composition of the PM would provoke different effects unique to the PM size fraction and with an association between exposure time, activation of AhR, and the expression of inflammatory genes. Human U937-derived macrophages were used to measure inflammatory biomarkers, cell viability and engulfment of PM. Particles across three size fractions - ultrafine (≥ 0.1 µm), fine (0.1-2.5 µm), and coarse (2.5-10 µm) were tested. RESULTS: Gene expression varied by PM source, size, and duration of exposure. PMIV typically induced a greater level of gene expression than PMPA of the same size fraction. For the 12-h experiments, ultrafine and coarse particle fractions were the most potent stimulators of gene expression compared to the control, irrespective of PM source. The results show that ultrafine/fine PMIV and fine PMPA typically produced the greatest increase in mRNA levels compared to the control in an AhR-dependent manner. CONCLUSIONS: Ultrafine and fine PM from both sites (PMIV and PMPA) preferentially engaged AhR-dependent signaling, whereas coarse PM activated NF-κB-mediated inflammatory pathways. Overall, this study demonstrates PM size- and time-dependent effects on inflammatory gene expression and highlights a distinction between AhR- and NF-κB-driven responses across PM fractions.