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Airway epithelial epidermal growth factor receptor mediates hogbarn dust-induced cytokine release but not Ca2+ response.

Authors
Dodmane-PR; Schulte-NA; Heires-AJ; Band-H; Romberger-DJ; Toews-ML
Source
Am J Respir Cell Mol Biol 2011 Oct; 45(4):882-888
NIOSHTIC No.
20039961
Abstract
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.
Keywords
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
Contact
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
CODEN
AJRBEL
CAS No.
7440-70-2
Publication Date
20111001
Document Type
Journal Article
Email Address
mtoews@unmc.edu
Funding Type
Grant
Fiscal Year
2012
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008539; B12072011
Issue of Publication
4
ISSN
1044-1549
Priority Area
Agriculture, Forestry and Fishing
Source Name
American Journal of Respiratory Cell and Molecular Biology
State
NE
Performing Organization
University of Nebraska
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