Zn2+ loading as a critical contributor to the circ_0008553-mediated oxidative stress and inflammation in response to PM2.5 exposures

Bing Yan , Jingzhou Wang , Jianbo Jia , Dujia Wang , Xiujiao Pan , Haiyan Xiong , Chengjun Li , Yiguo Jiang


Received July 05, 2021,Revised , Accepted November 12, 2021, Available online February 23, 2022

Volume 35,2023,Pages 451-461

Inflammation is a major adverse outcome induced by inhaled particulate matter with a diameter of ≤ 2.5 µm (PM2.5), and a critical trigger of most PM2.5 exposure-associated diseases. However, the key molecular events regulating the PM2.5-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 PM2.5-induced airway inflammation using three previously reported miRNAs through the starBase website. A novel circRNA circ_0008553 was identified to be responsible for the PM2.5-activated inflammatory response in human bronchial epithelial cells (16HBE) via inducing oxidative stress. Using a combinatorial model PM2.5 library, we found that the synergistic effect of the insoluble core and loaded Zn2+ 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 PM2.5-induced adverse outcomes.

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