Multi-omics analysis of the epigenetic effects of lipopolysaccharide-induced inflammation in Type II Pneumocytes

Chronic inflammation plays a central role in the pathogenesis of many lung diseases including asthma, SARS-COVID19, obstructive pulmonary disease (COPD), and lung cancer. Lipopolysaccharide (LPS) is an inflammatory agent produced by most Gram-negative bacteria and found in cigarette smoke. In a mouse model of inflammation, inhalation exposure to LPS induced COPD and increased the size and the multiplicity of lung tumors induced by tobacco-specific nitrosamines. In the present work, we employed a comprehensive multi-omics approach that monitored changes in DNA methylation/hydroxymethylation, gene expression, and global protein abundances in Type II pneumocytes of A/J mice following sub-chronic exposure to LPS. Overall design: Male and female A/J mice were intranasally treated with lipopolysaccharide (LPS) or PBS for 3 weeks, and 3 weeks followed by 4 weeks recovery. There are three mice in each treatment group. The mice were sacrificed after treatment and Alveolar type II epithelial cells (Type II pneumocytes) were isolated from the harvested lung tissues. DNA and RNA were extracted from the isolated Alveolar type II epithelial cells. DNA were used for genome wide mapping of 5mC and 5hmC and RNA were used for RNA-seq.