AIR POLLUTION EXPOSURE AND HEALTH EFFECTS: CELL-SHED MICROVESICLES AS CARRIERS FOR INTERCELLULAR COMMUNICATION

Air pollution exposure is a major problem worldwide and is associated with several diseases, but the molecular mechanisms underlying these associations still remain unknown. Obesity may increase susceptibility to the adverse effects of PM exposure, exacerbating the effects of PM on human health. Extracellular vesicles (EVs), which travel in body fluids and transfer molecular messages among tissues, might play an important role in connecting external exposures to health effects. We examined the effects of PM exposure in a population of 50 healthy subjects stratified for BMI on molecular alterations (Epstein Barr and Human endogenous retrovirus viral sequence methylation and telomere length modification), through a modulation of oxidative stress markers (mtDNA CN and 8OHdG). Our results revealed 8-hydroxydeoxyguanosine (8OHdG) decrease in response to short term exposure for both PM10 and PM2.5, in particular at day -3, -5, -6, -7. The effect was mainly determined by overweight subjects. On the contrary PM exposure was associated to an increased Telomere Length (TL), in overweight subjects only. The effect was maximum for day -3 and day -5 both for PM10 and PM2.5. Interestingly, both oxidative stress markers showed a negative association with TL again only in overweight subjects. DNA methylation has been associated to viral sequence reactivation, for this reason we have investigated methylation changes in Wp and Cp promoter for Epstein Barr virus (EBV) and Human Endogenous virus (HERV-w) in association with PM exposure observing a significant association at day -3 and day -4, -5, -6 respectively. The effect of PM on DNA methylation doesn’t seem to be modified by BMI of the subjects. This finding was also confirmed in vitro, as we treated Akata cell lines with PM and we observed an hypomethylation in EBV promoter, such as an increased expression of BZLF1, which is the first protein expressed in the reactivation of the lytic cycle of EBV.