FOXA1-TET1 Mediate the DNA Hypomethylation of IL-4 Is Involved in Dust Fall PM Induced Lung Inflammation.

PM has been linked to a variety of lung diseases. The objective of this study was to investigate the mechanism of lung inflammation caused by acute exposure to PM from the perspective of DNA methylation. Sprague-Dawley male rats were exposed to different concentrations of PM by non-exposure intratracheal instillation every other day for 3 times. Chemically modified si-Foxa1, si-Tet1, and si-NC were administered via the intratracheal instillation, followed by exposure to a medium concentration of PM. Fourteen days following the final exposure, serum, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for the appropriate tests. Acute exposure to PM resulted in infiltration of inflammatory cells and destruction of the alveolar structure. The levels of IL-4 and eotaxin-1 in serum and BALF were increased, while the levels of interferon-γ (IFN-γ) were decreased. In lung tissues, there was a decrease in the whole genome 5-mC and an increase in 5-hmC. The methylation level of the interleukin-4 (IL-4) DNA promoter CpG islands decreased, accompanied by an increase in the mRNA level. The protein expression of Forkhead box A1 (FOXA1) and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) was upregulated. Downregulation of FOXA1 and TET1 levels reversed those changes. PM induced the upregulation of FOXA1 and TET1 protein expression, which subsequently affected the DNA methylation levels of IL-4. This, in turn, promoted the release of IL-4 and led to pulmonary inflammation. This study provides insights into the potential DNA methylation regulatory mechanisms underlying lung inflammation induced by acute PM exposure.