Seasonal variations in the oxidative stress and inflammatory potential of PM_2.5 in Tehran using an alveolar macrophage model; The role of chemical composition and sources

Highlights

• DTT-ROS and AM-ROS activities exhibited clear seasonal pattern, with high levels produced for the cold season samples.

• Macrophage-based TNF-α secretion was over 2-fold higher in response to PM from the warm months.

• Vehicular emissions and residual oil were found to be the sources most associated with Tehran PM’s in vitro toxicity.

• mRNA of genes related to NRF2, NF-κB, and MAPK pathways showed substantial regulation.

Abstract

The current study was designed to assess the association between temporal variations in urban PM_2.5 chemical composition, sources, and the oxidative stress and inflammatory response in an alveolar macrophage (AM) model. A year-long sampling campaign collected PM_2.5 samples at the Sharif University in Tehran, Iran. PM-induced reactive oxygen species (ROS) production was measured both with an acellular dithiothreitol consumption assay (DTT-ROS; ranged from 2.1 to 9.3 nmoles min⁻¹ m⁻³) and an in vitro macrophage-mediated ROS production assay (AM-ROS; ranged from 125 to 1213 μg Zymosan equivalents m⁻³). The production of tumor necrosis factor alpha (TNF-α; ranged from ~60 to 518 pg TNF-α m⁻³) was quantified as a marker of the inflammatory potential of the PM. PM-induced DTT-ROS and AM-ROS were substantially higher for the colder months' PM (1.5-fold & 3-fold, respectively) compared with warm season. Vehicular emission tracers, aliphatic diacids, and hopanes exhibited moderate correlation with ROS measures. TNF-α secretion exhibited a markedly different pattern than ROS activity with a 2-fold increase in the warm months compared to the rest of the year. Gasoline vehicles and residual oil combustion were moderately associated with both ROS measures (R ≥ 0.67, p < 0.05), while diesel vehicles exhibited a strong correlation with secreted TNF-α in the cold season (R = 0.89, p < 0.05). mRNA expression of fourteen genes including antioxidant response and pro-inflammatory markers were found to be differentially modulated in our AM model. HMOX1, an antioxidant response gene, was up-regulated throughout the year. Pro-inflammatory genes (e.g. TNF-α and IL1β) were down-regulated in the cold season and displayed moderate to weak correlation with crustal elements (R > 0.5, p < 0.05). AM-ROS activity showed an inverse relationship with genes including SOD2, TNF, IL1β and IL6 (R ≥ −0.66, p < 0.01). Our findings indicate that Tehran's PM_2.5 has the potential to induce oxidative stress and inflammation responses in vitro. In the current study, these responses included NRF2, NF-κB and MAPK pathways.