Airway epithelial epidermal growth factor receptor mediates hogbarn dust-induced cytokine release but not Ca2+ response.
Dodmane-PR; Schulte-NA; Heires-AJ; Band-H; Romberger-DJ; Toews-ML
Am J Respir Cell Mol Biol 2011 Oct; 45(4):882-888
A subset of workers in swine confinement facilities develops chronic respiratory disease. An aqueous extract of dust from these facilities (hogbarn dust extract [HDE]) induces IL-6 and IL-8 release and several other responses in isolated airway epithelial cells. The cell membrane receptors by which HDE initiates these responses have not been identified. Because several other inhaled agents induce airway epithelial cell responses through epidermal growth factor receptor (EGFR) activation, we hypothesized that HDE would activate EGFRs and that EGFRs would be required for some of the responses to HDE. Exposure of Beas-2B cells to HDE caused EGFR phosphorylation and downstream ERK activation, and both responses were blocked by the EGFR-selective kinase inhibitor AG1478. AG1478 and EGFR-neutralizing antibody reduced HDE-stimulated IL-6 and IL-8 release by about half. Similar EGFR phosphorylation and requirement of EGFRs for maximal IL-6 and IL-8 release were found with primary isolates of human bronchial epithelial cells. Because HDE-stimulated IL-6 and IL-8 release involve the Ca(2+)-dependent protein kinase Ca, we hypothesized that HDE would induce intracellular Ca(2+) mobilization. HDE exposure induced intracellular Ca(2+) mobilization in Beas-2B cells and in primary cell isolates, but this response was neither mimicked by EGF nor inhibited by AG1478. Thus, HDE activates EGFRs and their downstream signaling, and EGFR activation is required for some but not all airway epithelial cell responses to HDE.
Respiratory-system-disorders; Animal-husbandry; Animal-husbandry-workers; Animals; Cellular-reactions; Antibody-response; Airborne-dusts; Airway-obstruction; Airway-resistance; Calcium-compounds; Dose-response; Cytotoxic-effects; Lung-cells; Drug-receptor; Drugs; Pharmacology; Immune-reaction; Immunology; Agricultural-workers; Farmers;
Author Keywords: airway epithelial cells; EGF receptors; hogbarn dust; cytokines; calcium
Myron L. Toews, Ph.D., Professor, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5800
Agriculture, Forestry and Fishing
American Journal of Respiratory Cell and Molecular Biology
University of Nebraska Medical Center, Omaha, Nebraska