The effects of fine particulate matter constituents on exhaled nitric oxide and DNA methylation in the arginase-nitric oxide synthase pathway

Background: Fine particulate matter (PM2.5) has been widely associated with airway inflammation represented by increased fractional concentration of exhaled nitric oxide (FeNO). However, it remains unclear whether various PM2.5 constituents have different impacts on FeNO and its production process from the arginase (ARG)-nitric oxide synthase (NOS) pathway. Objectives: To investigate the acute effects of PM2.5 constituents on FeNO and DNA methylation of genes involved. Methods: We conducted a longitudinal panel study among 43 young adults in Shanghai, China from May to October in 2016. We monitored the concentrations of 25 constituents of PM2.5. We applied the linear mixe-deffect model to evaluate the associations of PM2.5 constituents with FeNO and DNA methylation of the ARG2 and NOS2A genes. Results: Following PM2.5 exposure, NOS2A methylation decreased and ARG2 methylation increased only on the concurrent day, whereas FeNO increased most prominently on the second day. Nine constituents (OC, EC, K, Fe, Zn, Ba, Cr, Se, and Pb) showed consistent associations with elevated FeNO and decreased NOS2A methylation or increased ARG2 methylation in single-constituent models and models adjusting for PM2.5 total mass and collinearity. An interquartile range increase of these constituents was associated with respective decrements of 0.27-1.20 in NOS2A methylation (%5mC); increments of 0.48-1.56 in ARG2 methylation (%5mC); and increments of 7.12%-17.54% in FeNO. Conclusions: Our results suggested that OC, EC, and some metallic elements may be mainly responsible for the development and epigenetic regulation of airway inflammatory response induced by short-term PM2.5 exposure.