Cytotoxicity And HIF-1α Mediated Regulation Of IL-6in Vascular Endothelial ECV304Cells Exposed To PM2.5

Fine particulate matter (PM2.5, less than2.5nm in aerodynamic diameter) is themain component of air pollution and has major negative effects on the cardiovascularsystem. Recent evidence showed that hypoxia-inducible factor-1α (HIF-1α) and IL-6maybe involved in cardiovascular disease, but the relationship among IL-6, HIF-1α andcardiovascular disease induced by PM2.5is still unclear. In the present study, analysis ofPM2.5collected in Beijing, China for six months showed that it was mostly composed ofAl, Fe, Ca, Zn and PHA (5,6), while other components accounted for less than1%. PM2.5was observed to damage and increase plasma membrane permeability as well asdose-dependently induce HIF-1α gene expression in the ECV-304endothelial cell line. Inevaluating levels of several cytokines in both culture medium and lysate of ECV-304cellsexposed to PM2.5, only the expression of IL-6was significantly different between thecontrol and treatment groups (P=0.009). Interestingly, when siRNA was employed toinhibit HIF-1α expression in ECV304cells treated with PM2.5, IL-6expression wassignificantly increased at both the mRNA and protein levels (P=0.016). Furthermore,treatment of ECV304cells with exogenous IL-6significantly increased both HIF-1αmRNA and protein levels (P=0.0000). Overall, our results demonstrated that PM2.5couldcause Cytotoxicity and cell membrane damage on ECV304cell. And HIF-1α is directlyrelated to PM2.5-induced damage in the cardiovascular system, and HIF-1α expression isassociated with IL-6production in ECV-304cells. Therefore, HIF-1α may act as a negativefeedback regulator in PM2.5-induced IL-6expression and release in endothelial cells.