FOXA1-TET1 Mediate the DNA Hypomethylation of IL-4 Is Involved in Dust Fall PM_2.5 Induced Lung Inflammation

Area of Science:

• Environmental Health
• Molecular Biology
• Toxicology

Background:

• Particulate matter (PM2.5) is a major air pollutant linked to respiratory diseases.
• The precise mechanisms by which PM2.5 induces lung inflammation, particularly involving epigenetic modifications, require further elucidation.

Purpose of the Study:

• To investigate the role of DNA methylation in acute lung inflammation triggered by PM2.5 exposure.
• To explore the involvement of Forkhead box A1 (FOXA1) and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) in PM2.5-induced pulmonary inflammation.

Main Methods:

• Rats were exposed to varying concentrations of PM2.5 via intratracheal instillation.
• Intervention with si-Foxa1, si-Tet1, or si-NC was performed, followed by PM2.5 exposure.
• Serum, bronchoalveolar lavage fluid (BALF), and lung tissues were analyzed for inflammatory markers and DNA methylation patterns.

Main Results:

• PM2.5 exposure led to inflammatory cell infiltration and alveolar structure damage.
• Increased levels of IL-4 and eotaxin-1, with decreased IFN-γ, were observed in serum and BALF.
• Global DNA methylation (5-mC) decreased, while 5-hydroxymethylation (5-hmC) increased, particularly at the IL-4 promoter.
• Upregulation of FOXA1 and TET1 protein expression correlated with increased IL-4 mRNA and protein, and subsequent inflammation.
• Downregulation of FOXA1 and TET1 reversed these inflammatory changes.

Conclusions:

• PM2.5 exposure induces lung inflammation through epigenetic regulation of IL-4 via FOXA1 and TET1.
• This study highlights a novel DNA methylation pathway contributing to PM2.5-mediated pulmonary inflammation.
• Targeting FOXA1 and TET1 may offer therapeutic strategies for PM2.5-induced lung injury.