Effect of elevated carbon dioxide on bronchial epithelial innate immune receptor response to organic dust from swine confinement barns

Authors

D. Schneberger, University of Nebraska Medical Center
D. Cloonan, University of Nebraska Medical Center
J.M. DeVasure, University of Nebraska Medical CenterFollow
K.L. Bailey, Research Service, Veterans Administration Nebraska Western Iowa Health Care System, Omaha, NE
D.J. Romberger, Research Service, Veterans Administration Nebraska Western Iowa Health Care System, Omaha, NE
Todd A. Wyatt, University of Nebraska Medical CenterFollow

Date of this Version

2015

Document Type

Article

Citation

International Immunopharmacology 27 (2015) 76–84

Comments

U.S. Government Work

Abstract

Hypercapnia is known to have immunoregulatory effects within the lung. Cell culture systems demonstrate this in both macrophages and alveolar cell lines, suggesting that the alveoli are affected by changes in CO₂ levels.We hypothesized that hypercapnia would also modulate human bronchial epithelial cell immune responses. Innate immune responses to Pam3CSK4 (TLR2 ligand), LPS (TLR4 ligand) and a complex innate immune stimulus, an extract from the organic dust of swine confinement barns (barn dust extract or BDE),were tested in a human bronchial epithelial cell line, BEAS-2B. Both TLR ligands showed a decrease in IL-6 and IL-8 production, and an increase in MCP-1 in response to elevated CO₂ indicating an enhancement in cytokine production to hypercapnia. This change was not reflected in expression levels of TLR receptor RNA which remained unchanged in response to elevated CO₂. Interestingly, barn dust showed an increase in IL-6, IL-8 and MCP-1 response at 9% CO₂, suggesting that elevated CO₂ exerts different effects on different stimuli. Our results show that airway epithelial cell immune responses to barn dust respond differently to hypercapnic conditions than individual TLR ligands.