Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells

In the lungs of cystic fibrosis patients, overproduction of mucus leads to morbidity and mortality by obstructing airflow and shielding bacteria from antibiotics. Here we demonstrate that overproduction of mucus is a direct result of the activation of mucin gene expression by Grampositive bacteria. Bacterial lipoteichoic acid activates the platelet-activating factor receptor, which is G protein-coupled. This results in activation of a disintegrin and metalloproteinase (ADAM10), kuzbanian, cleavage of pro heparin-binding epidermal growth factor and activation of the epidermal growth factor receptor. Unlike responses in macrophages, the epithelial-cell response to lipoteichoic acid does not require Toll-like receptor 2 or 4.