Organic Dust Epithelial PKC Activation and Airway Disease.

摘要

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 concentrated animal feeding operations (CAFOs). Persons exposed to hog CAFOs have airway inflammation and an increased incidence of COPD. Although many substances are present in hog barn dust that induce inflammation, 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 within the airways 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. Previously, 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. The objective of this proposal was 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 lysophosphatidic acid (LPA), an important lipid mediator, in modulating dust effects on PKC and inflammatory responses.