Personal Ozone Exposure and Respiratory Inflammatory Response: The Role of DNA Methylation in the Arginase–Nitric Oxide Synthase Pathway

Little is known regarding the molecular mechanisms behind respiratory inflammatory response induced by ozone. We performed a longitudinal panel study with four repeated measurements among 43 young adults in Shanghai, China from May to October in 2016. We collected buccal samples and measured the fractional exhaled nitric oxide (FeNO) after 3-day personal ozone monitoring. In buccal samples, we measured concentrations of inducible nitric oxide synthase (iNOS) and arginase (ARG), and DNA methylation of <i>NOS2A</i> and <i>ARG2</i>. We used linear mixed-effect models to analyze the effects of ozone on FeNO, two enzymes and their DNA methylation. A 10 ppb increase in ozone (lag 0–8 h) was significantly associated with a 3.89% increase in FeNO, a 36.33% increase in iNOS, and a decrease of 0.36 in the average methylation (%5mC) of <i>NOS2A</i>. Ozone was associated with decreased ARG and elevated <i>ARG2</i> methylation, but the associations were not significant. These effects were more pronounced among allergic subjects than healthy subjects. The effects were much stronger when using personal exposure monitoring than fixed-site measurements. Our study demonstrated that personal short-term exposure to ozone may result in acute respiratory inflammation, which may be mainly modulated by <i>NOS2A</i> hypomethylation in the arginase–nitric oxide synthase pathway