Identification Of Key Toxic Heavy Metal Components And Underlying Mechanisms For PM_2.5-Induced Inflammation In 16HBE Cells

In recent years,large-scale haze weather and severe air pollution have continuously occurred in many cities in North China,which has been associated with increased morbidity of a variety of human diseases including respiratory diseases,cardiovascular diseases and cancer.Fine particulate matter(aerodynamic diameters of 2.5μm or smaller,PM_2.5)with the characteristics of small size,large specific surface area,strong penetration and loadings of various pollutants,has become a serious risk factor to human health.PM_2.5can induce cell death,oxidative stress,DNA damage and inflammation.Inflammation is the main adverse outcome induce by inhaled PM_2.5,and a critical trigger of most PM_2.5exposure-associated diseases.The toxicity of PM_2.5largely depends on the composition of pollutants adsorbed by PM_2.5,which varies greatly in different regions.In North China,concentrations of PM_2.5in autumn or winter are much higher than that in summer.This is due to the increased fossil fuel combustion for heating in winter and the longer residence time of airborne PM_2.5in the air because of low temperature.Moreover,PM_2.5particles in autumn or winter have much higher pollutant loadings,showing higher toxic effects than that in summer.Thus,it is urgently in need for us to identify the key toxic components of PM_2.5and establish the cause-effect relationship between PM_2.5components and health effects.Inconsistent results may be obtained from different epidemiological studies exploring the correlation between PM_2.5and respiratory diseases.This may be due to the time-and region-dependent variety of PM_2.5components.Therefore,it is of great importance to identify the key toxic components and reveal the underlying mechanism of PM_2.5-induced toxicity.In this study,we aim to solve the following scientific problems:Firstly,among the various metal ions loaded on Jinan PM_2.5particles,what component（s）contribute the greatest to the PM_2.5-induced inflammation?Secondly,whether and how could non-coding RNA,in particular circRNA,regulate the PM_2.5-induced inflammatory response in human bronchial epithelial（16HBE）cells?Main findings of this study are listed as followed.1)A total of 12 potential carcinogenic heavy metals listed in the EPA standard of the United States were selected as the detection objects for the characterization of the loadings of metal ions on Jinan PM_2.5particles.Zn and Cu,whose limitations of concentration in the air have not been involved in the present ambient air quality standards of China（GB 3095-2012）,have the highest contents in Jinan PM_2.5.While the content of Cd and As was slightly higher than the WHO standards,the contents of Pb,Cr,Ni and V were far lower than the WHO standards.2)Using a combinatorial model PM_2.5library,we found that the synergistic effect of the insoluble core and loaded Zn²⁺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 PM_2.5exposures.Our findings provide experimental basis for early detection,risk assessment and protective treatment after exposure to PM_2.5,and has important implications for targeted prevention and control of PM_2.5.