Submitted on July 16, 2007
Accepted on October 7, 2007
Hog barn dust slows airway epithelial cell migration in vitro through a PKC
-dependent mechanism
Rebecca E Slager1, Diane S. Allen-Gipson1, Alexi Sammut1, Art Heires1, Jane DeVasure1, Susanna G. Von Essen2, Debra J. Romberger3, and Todd A Wyatt3*
1 Internal Medicine-Pulmonary, Critical Care, Sleep & Allergy Section, University of Nebraska Medical Center, Omaha, Nebraska, United States
2 Internal Medicine-Pulmonary, Critical Care, Sleep & Allergy Section, University of Nebraska Medical Center, Omaha, Nebraska, United States; College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska, United States
3 Internal Medicine-Pulmonary, Critical Care, Sleep & Allergy Section, University of Nebraska Medical Center, Omaha, Nebraska, United States; Research Service, Department of Veterans Affairs Medical Center, Omaha, Nebraska, United States
* To whom correspondence should be addressed. E-mail: twyatt{at}unmc.edu.
Agricultural work and other occupational exposures are responsible for approximately 15% of chronic obstructive pulmonary disease (COPD). COPD involves airway remodeling in response to chronic lung inflammatory events and altered airway repair mechanisms. However, the effect of agricultural dust exposure on signaling pathways that regulate airway injury and repair has not been well characterized. A key step in this process is migration of airway cells to restore epithelial integrity. We have previously shown that agents which activate the critical regulatory enzyme protein kinase C (PKC) slow cell migration during wound repair. Based on this observation and direct kinase measurements which demonstrate that dust extract from hog confinement barns (HDE) specifically activates the PKC isoforms PKC
and PKC
, we hypothesized that HDE would slow wound closure time in airway epithelial cells. We utilized the human bronchial epithelial cell line BEAS-2B and transfected BEAS-2B cell lines that express dominant negative (DN) forms of PKC isoforms to demonstrate that HDE slows wound closure in BEAS-2B and PKC DN cell lines. However, in PKC DN cells, wound closure following HDE treatment is not significantly different than media-treated cells. These results suggest that the PKC isoform is an important regulator of cell migration in response to agricultural dust exposure.
