Identification of multiple dysregulated metabolic pathways by GC-MS-based profiling of lung tissue in mice with PM2.5-induced asthma

Abstract

The risk of development of asthma, a multi-faceted chronic disease, increases as a result of exposure to PM2.5. However, the mechanism underlying asthma-related metabolic changes caused by PM2.5 exposure is unclear. Here, we investigated the major metabolic changes, metabolic pathways involved, and underlying molecular mechanisms in mice with PM2.5 exposure-induced asthma. Forty-eight adult female mice were randomly assigned to control (C), low concentration-PM2.5 exposure: 0.50 mg kg−1 (L), medium concentration-PM2.5 exposure: 1.58 mg kg−1 (M), and high concentration-PM2.5 exposure: 4.98 mg kg−1 (H) groups. M and H groups presented significantly higher IL-4, IL-8, IL-1β, IL-5, IL-13, and OVA-specific IgE levels, and significantly lower IFN-γ levels, than the C group, as well as significantly increased eosinophil count and MUC5AC expression in the lung tissue. These findings indicate that exposure to medium and high concentrations of PM2.5 induced asthma in mice. Statistical analyses identified 13 asthma-related major metabolites, which were analyzed by gas chromatography-mass spectrometry (GC-MS). Meta Mapp Software revealed 4 major metabolic pathways. PM2.5-induced ATP requirement and oxidative stress may perturb metabolic processes in asthma. The present findings increase our understanding of the toxic effect of PM2.5 in the development of asthma and identify potentially useful biomarkers.