Altered secretome by diesel exhaust particles and lipopolysaccharide in primary human nasal epithelium

Abstract

Airway epithelial cells can actively participate in the defense against environmental pathogens to elicit local or systemic inflammation. Diesel exhaust particles (DEP), a main component of urban air pollution with particulate matter, are associated with the occurrence of acute and chronic upper airway inflammatory diseases. We sought to investigate the effect of DEP alone or in combination with lipopolysaccharide on the secretome in the primary human nasal epithelium (PHNE) and to find potential biomarkers to relate DEP exposure to upper airway inflammatory diseases. PHNE was cultured at an air-liquid interface to create a differentiated invivo-like model. Secreted proteins (secretome) on the bottom media of the PHNE were analyzed by mass spectrometry-based label-free quantitative proteomics and ELISA. Considerably more differentially expressed secreted proteins were identified in response to DEP plus lipopolysaccharide than to DEP alone. Some canonical pathways related to inflammation and cancer such as the p53, β-catenin, and extracellular signal-regulated kinase 1/2 pathways were involved. Among differentially expressed secreted proteins, leukemia inhibitory factor was also detected at a high level in the middle ear effusions of otitis media patients, and the leukemia inhibitory factor level was significantly correlated with daily mean mass concentrations of atmospheric particulate matter averaged over 8 days before sample collection. Apical stimulation with DEP and lipopolysaccharide can significantly alter the basal secretome in PHNE, and this alteration can be reflected by surrounding inflammation with effusion of fluids invivo such as middle ear effusions in otitis media patients.