Exposure to organic dusts is a cause of airway disease, including chronic obstructive pulmonary disease (COPD). As many as 20% of COPD cases are attributed to occupational exposures. In rural areas, an important source of dust exposure occurs in hog confinement barns. Persons exposed to hog barns have airway inflammation and an increased incidence of COPD. Although many substances are present in hog barn dust that induces inflammation including endotoxins, actual mechanisms leading to COPD are not well defined. Understanding mechanisms of hog barn dust-induced airway disease is relevant in developing both targeted treatment and prevention strategies. Epithelial cells respond to inhaled agents with the release of cytokines that recruit and activate inflammatory cells and expression of molecules that serve as receptors and ligands for interactions with other cells. We observed that hog barn dust extract (HDE) augments human airway epithelial protein kinase C (PKC) activation, resulting in IL-8 and IL-6 release and increased ICAM-1 expression, mediating inflammatory cell adhesion to airway epithelium in vitro. Using an intranasal exposure to HDE in mice, we observed an increase in airway epithelial PKC activation and inflammatory responses in vivo. We recently observed that epithelial cell exposure to HDE results in an increase of the lipid mediator lysophosphatidic acid (LPA). Treatment with phospholipase B to inactivate LPA inhibits HDE-stimulated IL-6 and IL-8 release. The role of LPA induced by hog barn dust in directing airway inflammation is not known. The objective of this proposal is to define mechanisms by which hog barn dust activates epithelial cell PKC and the role of PKC in airway inflammation associated with chronic bronchitis occurring in confinement facility workers and to determine the role of hog barn dust-related LPA, an important lipid mediator, in modulating dust effects on PKC and inflammatory responses. We will address our hypothesis with these specific aims: 1) Determine the biochemical nature and specific identity of factor(s) in HDE that activate epithelial cell PKC and identify the specific PKC isoenzymes activated by HDE and these factors. 2) Establish how HDE-associated lysophosphatidic acid (LPA) modulates HDE-induced epithelial cell PKC activity and IL-8/IL-6 release. 3) Identify mechanisms by which HDE augmentation of epithelial cell PKC In vitro mediates recruitment and adhesion of inflammatory cells to airway epithelium in vitro. 4) Determine how HDE modulates airway epithelial PKC activation and inflammatory responses in vivo utilizing an animal model of exposure, including testing the potential role of LPA. ? ? ?

National Institute of Health (NIH)
National Institute for Occupational Safety and Health (NIOSH)
Research Project (R01)
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Safety and Occupational Health Study Section (SOH)
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Robison, William
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University of Nebraska Medical Center
Internal Medicine/Medicine
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United States
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Weissenburger-Moser, Lisa; Meza, Jane; Yu, Fang et al. (2017) A principal factor analysis to characterize agricultural exposures among Nebraska veterans. J Expo Sci Environ Epidemiol 27:214-220
Wyatt, Todd A; Canady, Kerry; Heires, Art J et al. (2017) Alcohol Inhibits Organic Dust-induced ICAM-1 Expression on Bronchial Epithelial Cells. Safety (Basel) 3:
Poole, Jill A; Mikuls, Ted R; Duryee, Michael J et al. (2017) A role for B cells in organic dust induced lung inflammation. Respir Res 18:214
Gerald, Carresse L; Romberger, Debra J; DeVasure, Jane M et al. (2016) Alcohol Decreases Organic Dust-Stimulated Airway Epithelial TNF-Alpha Through a Nitric Oxide and Protein Kinase-Mediated Inhibition of TACE. Alcohol Clin Exp Res 40:273-83
Poole, Jill A; Wyatt, Todd A; Romberger, Debra J et al. (2015) MyD88 in lung resident cells governs airway inflammatory and pulmonary function responses to organic dust treatment. Respir Res 16:111
Poole, Jill A; Anderson, Leigh; Gleason, Angela M et al. (2015) Pattern recognition scavenger receptor A/CD204 regulates airway inflammatory homeostasis following organic dust extract exposures. J Immunotoxicol 12:64-73
Romberger, Debra J; Heires, Art J; Nordgren, Tara M et al. (2015) Proteases in agricultural dust induce lung inflammation through PAR-1 and PAR-2 activation. Am J Physiol Lung Cell Mol Physiol 309:L388-99
Nordgren, Tara M; Bauer, Christopher D; Heires, Art J et al. (2015) Maresin-1 reduces airway inflammation associated with acute and repetitive exposures to organic dust. Transl Res 166:57-69
Schneberger, D; Gordon, J R; DeVasure, J M et al. (2015) CXCR1/CXCR2 antagonist CXCL8(3-74)K11R/G31P blocks lung inflammation in swine barn dust-instilled mice. Pulm Pharmacol Ther 31:55-62
Poole, Jill A; Romberger, Debra J; Wyatt, Todd A et al. (2015) Age Impacts Pulmonary Inflammation and Systemic Bone Response to Inhaled Organic Dust Exposure. J Toxicol Environ Health A 78:1201-16

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