Personal Fine Particulate Matter Constituents, Increased Systemic Inflammation, and the Role of DNA Hypomethylation

Limited evidence is available on the effects of various fine particulate matter (PM_2.5) components on inflammatory cytokines and DNA methylation. We examined whether 16 PM_2.5 components are associated with changes in four blood biomarkers, that is, tumor necrosis factor-α (TNF-α), soluble cluster of differentiation 40 ligand (sCD40L), soluble intercellular adhesion molecule-1 (sICAM-1), and fibrinogen, as well as their corresponding DNA methylation levels in a panel of 36 healthy college students in Shanghai, China. We used linear mixed-effect models to evaluate the associations, with controls of potential confounders. We further conducted mediation analysis to evaluate the potential mediation effects of components on inflammatory markers through change in DNA methylation. We observed that several components were consistently associated with TNF-α and fibrinogen as well as their DNA hypomethylation. For example, an interquartile range increase in personal exposure to PM_2.5-lead (Pb) was associated with 65.20% (95% CI: 37.07, 99.10) increase in TNF-α and 2.66 (95% CI: 37.07, 99.10) decrease in TNF-α methylation, 30.51% (95% CI: 0.72, 69.11) increase in fibrinogen and 1.25 (95% CI: 0.67, 1.83) decrease in F3 methylation. PM_2.5 components were significantly associated with sICAM-1 methylation but not with sICAM-1 protein. DNA methylation mediated 19.89%-41.75% of the elevation in TNF-α expression by various PM_2.5 constituents. Our findings provide clues that personal PM_2.5 constituents exposure may contribute to increased systemic inflammation through DNA hypomethylation.