69 Activation of the Aryl Hydrocarbon Receptor - a Major mode of Combustion Particle Toxicity?

Abstract Combustion-derived particles constitute an important part of the fine fraction of particulate matter with aerodynamic diameter less than 2.5 microns (PM2.5) and are considered central for the adverse effects of air pollution. Understanding the mechanisms of combustion particle toxicity may shed light on the components and characteristics of outdoor air PM driving adverse health effects. This may also enable more targeted and efficient policies to improve air quality and promote health and wellbeing. The aryl hydrocarbon receptor (AhR) is a ligand dependent transcription factor, originally discovered for its ability to bind polycyclic aromatic hydrocarbons (PAHs) and dioxin-like compounds and regulate PAH metabolism. It is now clear that AhR regulates a variety of biological and toxicological responses, overlapping to a considerable degree with the effects of combustion PM and ambient PM2.5. Studies from our lab and others also suggest that AhR activation is among the most sensitive responses to combustion PM exposure, induced at orders of magnitude lower concentrations than many other endpoints. This talk will discuss the potential role of the AhR and PAHs in combustion PM toxicity based on previous and ongoing work, with a main focus on intracellular signalling and regulation of inflammatory reactions in lung epithelial cells and vascular endothelial cells.