Inflammation is one of the major adverse effects of fine particulate matter (PM<sub>2.5</sub>) on the lung system; however, its mechanisms remain unclear. Rats were exposed to different concentrations of PM<sub>2.5</sub> to investigate the mechanism of short-term exposure-induced lung inflammation. The regulation of PI3K-Akt and DNA methyltransferase 3b (DNMT3b) was assessed by using a PI3K inhibitor and a DNA methyltransferase inhibitor. We found that PM<sub>2.5</sub> could decrease interferon-γ (IFN-γ) levels and increase interleukin 4 (IL-4), IL-5 and IL-13 levels in bronchoalveolar lavage fluid (BALF) to promote eosinophil infiltration and eventually lead to allergic pulmonary inflammation. Moreover, the CpG island methylation rate of the IFN-γ promoter and the protein expression of DNMT3b, PI3K and p-Akt were increased in lung tissues after PM<sub>2.5</sub> exposure. Both inhibitors reversed the CpG island hypermethylation of IFN-γ. In conclusion, in PM<sub>2.5</sub>-induced lung injury, the activated PI3K-Akt pathway, via an increase in DNMT3b expression, is involved in CpG hypermethylation of the IFN-γ gene promoter.
Amaia Lujambio, Santiago Ropero, Esteban Ballestar, Mario F. Fraga, Celia Cerrato, Fernando Setién, Sara Casado, Ana Suárez‐Gauthier, Montse Sánchez‐Céspedes, Anna Gitt, Inmaculada Spiteri, Partha Pratim Das, Carlos Caldas, Eric A. Miska, Manel Esteller
Amaia Lujambio, Santiago Ropero, Esteban Ballestar, Mario F. Fraga, Celia Cerrato, Fernando Setién, Sara Casado, Ana Suárez‐Gauthier, Montse Sánchez‐Céspedes, Anna Gitt, Inmaculada Spiteri, Partha Pratim Das, Carlos Caldas, Eric A. Miska, Manel Esteller
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