Zn^(2+) loading as a critical contributor to the circ_0008553-mediated oxidative stress and inflammation in response to PM_(2.5) exposures

Inflammation is a major adverse outcome induced by inhaled particulate matter with a diameter of≤2.5μm(PM_(2.5)),and a critical trigger ofmost PM_(2.5) exposure-associated diseases.However,the key molecular events regulating the PM_(2.5)-induced airway inflammation are yet to be elucidated.Considering the critical role of circular RNAs(circRNAs)in regulating inflammation,we predicted 11 circRNAs that may be involved in the PM_(2.5)-induced airway inflammation using three previously reportedmiRNAs through the starBasewebsite.A novel circRNA circ_0008553 was identified to be responsible for the PM_(2.5)-activated inflammatory response in human bronchial epithelial cells(16HBE)via inducing oxidative stress.Using a combinatorial model PM_(2.5) library,we found that the synergistic effect of the insoluble core and loaded Zn^(2+)ions at environmentally relevant concentrations was the major contributor to the upregulation of circ_0008553 and subsequent induction of oxidative stress and inflammation in response to PM2.5 exposures.Our findings provided new insight into the intervention of PM_(2.5)-induced adverse outcomes.