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 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.
Lemjabbar
Hassan
H
Biomedical Sciences Program, Cardiovascular Research Institute and Department of Anatomy, University of California, San Francisco, California, USA.
Basbaum
Carol
C
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
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