Toll-like receptor 2 is upregulated by hog confinement dust in an IL-6-dependent manner in the airway epithelium.
Bailey KL; Poole JA; Mathisen TL; Wyatt TA; Von Essen SG; Romberger DJ
Am J Physiol, Lung Cell Mol Physiol 2008 Jun; 294(6):L1049-1054
Toll-like receptor 2 is upregulated by hog confinement dust in an IL-6-dependent manner in the airway epithelium. Am J Physiol Lung Cell Mol Physiol 294: L1049-L1054, 2008. First published March 21, 2008; doi:10.1152/ajplung.00526.2007. Hog confinement workers are at high risk to develop chronic bronchitis as a result of their exposure to organic dust. Chronic bronchitis is characterized by inflammatory changes of the airway epithelium. A key mediator in inflammation is Toll-like receptor 2 (TLR2). We investigated the role of TLR2 in pulmonary inflammation induced by hog confinement dust. Normal human bronchial epithelial cells (NHBE) were grown in culture and exposed to hog confinement dust extract. Hog confinement dust upregulated airway epithelial cell TLR2 mRNA in a concentration- and time-dependent manner using real-time PCR. There was a similar increase in TLR2 protein at 48 h as shown by Western blot. TLR2 was upregulated on the surface of airway epithelial cells as shown by flow cytometry. A similar upregulation of pulmonary TLR2 mRNA and protein was shown in a murine model of hog confinement dust exposure. Hog confinement dust is known to stimulate epithelial cells to produce IL-6. To determine whether TLR2 expression was being regulated by IL-6, the production of IL-6 was blocked using an IL-6- neutralizing antibody. This resulted in attenuation of the dust-induced upregulation of TLR2. To further demonstrate the importance of IL-6 in the regulation of TLR2, NHBE were directly stimulated with recombinant human IL-6. IL-6 alone was able to upregulate TLR2 in airway epithelial cells. Hog confinement dust upregulates TLR2 in the airway epithelium through an IL-6-dependent mechanism. Toll-like receptor 2 (TLR2), which recognizes peptidoglycan, lipoteichoic acid, and zymosan, is expressed in airway epithelium and is a key mediator in lung innate immunity. When TLR2 is activated, it initiates the cellular inflammatory response to Gram-positive microbial invasion. In this study, we investigated the effect of hog confinement dust exposure on expression of TLR2 mRNA and protein in an in vitro model of airway epithelial cells and in an in vivo murine model of hog confinement dust exposure. We have previously shown that IL-6 is rapidly secreted by the airway epithelium in response to hog confinement dust stimulation. This led us to hypothesize that IL-6 may be a critical hog confinement dust mediator that stimulates TLR2 expression in the airway epithelium.
Organic-dusts; Pulmonary-system; Pulmonary-system-disorders; Pulmonary-disorders; Respiratory-system-disorders; Diseases; Exposure-levels; Animals; Farmers; Agriculture; Agricultural-industry; Bacterial-dusts; Bacteria; Workers; Work-environment; Epidemiology; Demographic-characteristics; Age-groups; Organic-compounds; Lung-function; Lung; Humans; Men; Women; Lung-disorders;
Author Keywords: chronic bronchitis; normal human bronchial epithelial cells
Kristina L. Bailey, MD, Pulmonary, Critical Care, Sleep and Allergy Section, Dept. of Internal Medicine, 985300 Nebraska Medical Center, Omaha, NE 68198-5300
Agriculture, Forestry and Fishing
American Journal of Physiology: Lung Cellular and Molecular Physiology
University of Nebraska Medical Center, Omaha, Nebraska