Pseudomonas Elastase-Induced Inflammation in Cystic Fibrosis Lungs

Pseudomonas aeruginosa is a major contributor to chronic inflammation in cystic fibrosis lungs. In terms of pathogenesis, P. aeruginosa elastase (PE) increases epithelial paracellular permeability and activates epidermal growth factor receptor (EGFR) and downstream MAPK/ERK signaling cascade in vitro. We used EGFR-expressing human pulmonary epithelial cells to investigate the mechanism of PE-induced EGFR activation. We hypothesized that PE activates EGFR indirectly through soluble pro-ligands secreted by epithelial cells. Recombinant PE (rPE) was encapsulated inside virus like particles to serve as a mediator of PE-EGFR interactions. We employed a cell culture model and biochemical analysis including SDS-PAGE and Western blotting. Densitometric analysis of phosphorylated and total EGFR and ERK confirmed that encapsulated rPE did not activate the MAPK/ERK pathway. We conclude that direct contact between elastase and insoluble/membrane bound ligand(s) is the likely candidate for EGFR activation. These findings may provide an opportunity for novel drug development against P. aeruginosa-induced inflammation.