Fig. 2

Epigenetic mechanisms mediate DEP effects on asthma pathogenesis. Lung epithelial cells recognize polycyclic aromatic hydrocarbons present in diesel exhaust particles (DEPs) via the aryl hydrocarbon receptor (AhR), promoting cytochrome P450 family 1 A1 (CYP1A1)-mediated and iNOS-mediated detoxification through altering methylation. Failure to detoxify results in oxidative stress, which may upregulate TETs and downregulate DNMTs through the crosstalk between AhR and HIF1-α and directly lead to secretion of chemokines (eosinophils/neutrophils) and cytokines involved in TH17 and TH2 differentiation (TSLP), Treg differentiation and B cell function, all contributing to airway inflammation. The secretion of these chemokines and cytokines can also be triggered by repair cytokines (amphiregulin, TGFα) signaling through the epidermal growth factor receptor (EGFR), p38 mitogen-activated protein kinase, and NF-κB, which can be augmented by demethylation and upregulation through TET proteins and DNMTs. DEP promotes allergic airway inflammation by upregulating the expression of the Jagged1/Notch1 pathway in dendritic cells (DC) in an AhR dependent manner in concert with allergens. DEP may also regulate DNMT and TET expression in dendritic cells and macrophages through the AhR pathway, enhancing airway inflammation in presence of allergens. DEP diesel exhaust particle; OVA ovalbumin; TSLP thymic stromal lymphopoietin