Seasonal variations in the oxidative stress and inflammatory potential of PM2.5 in Tehran using an alveolar macrophage model; The role of chemical composition and sources

The current study was designed to assess the association between temporal variations in urban PM2.5 chemical composition, sources, and the oxidative stress and inflammatory response in an alveolar macrophage (AM) model. A year-long sampling campaign collected PM2.5 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 mu g Zymosan equivalents m(-3)). The production of tumor necrosis factor alpha (TNF-alpha; ranged from similar to 60 to 518 pg TNF-alpha 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-alpha 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-alpha 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-alpha and IL1 beta) 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, IL1 beta and IL6 (R=-0.66, p < 0.01). Our findings indicate that Tehran's PM2.5 has the potential to induce oxidative stress and inflammation responses in vitro. In the current study, these responses included NRF2, NF-kappa B and MAPK pathways.