title: Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells.
abstract: 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 Gram-positive 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.
authors.affiliation: Biomedical Sciences Program, Cardiovascular Research Institute and Department of Anatomy, University of California, San Francisco, California, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Lemjabbar
authors.forename: Carol
authors.initials: C
authors.lastname: Basbaum
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D019483:Disintegrins / Q000378:metabolism; D029721:Drosophila Proteins; D010450:Endopeptidases / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology*; D066246:ErbB Receptors / Q000235:genetics; D006094:Gram-Positive Bacteria / Q000472:pathogenicity; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D008957:Models, Genetic; D055262:Mucin-2; D009077:Mucins / Q000096:biosynthesis; D009093:Mucus / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction; D013203:Staphylococcal Infections / Q000473:pathology; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D013682:Teichoic Acids / Q000494:pharmacology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D015533:Transcriptional Activation
chemical_list: D019483:Disintegrins; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; C524625:MUC2 protein, human; D008562:Membrane Glycoproteins; D055262:Mucin-2; D009077:Mucins; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C495342:TLR2 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; C039351:platelet activating factor receptor; C009900:lipoteichoic acid; D066246:ErbB Receptors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C100953:KUZ protein, Drosophila; D008666:Metalloendopeptidases