title: Hog barn dust slows airway epithelial cell migration in vitro through a PKCalpha-dependent mechanism.
abstract: 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 that activate the critical regulatory enzyme protein kinase C (PKC) slow cell migration during wound repair. Based on this observation and direct kinase measurements that demonstrate that dust extract from hog confinement barns (HDE) specifically activates the PKC isoforms PKCalpha and PKCepsilon, 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 PKCepsilon DN cell lines. However, in PKCalpha DN cells, wound closure following HDE treatment is not significantly different than media-treated cells. These results suggest that the PKCalpha isoform is an important regulator of cell migration in response to agricultural dust exposure.
authors.affiliation: Department of Internal Medicine, Pulmonary and Critical Care Medicine Section, University of Nebraska Medical Center, Omaha, NE 68198-5300, USA.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Slager
authors.forename: Diane S
authors.initials: DS
authors.lastname: Allen-Gipson
authors.forename: Alexi
authors.initials: A
authors.lastname: Sammut
authors.forename: Art
authors.initials: A
authors.lastname: Heires
authors.forename: Jane
authors.initials: J
authors.lastname: DeVasure
authors.forename: Susanna
authors.initials: S
authors.lastname: Von Essen
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Romberger
authors.forename: Todd A
authors.initials: TA
authors.lastname: Wyatt
mesh_terms: D001980:Bronchi / Q000166:cytology* / Q000201:enzymology*; D002460:Cell Line; D002465:Cell Movement; D004391:Dust; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology* / Q000201:enzymology*; D005799:Genes, Dominant; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D014162:Transfection; D014945:Wound Healing
chemical_list: D004391:Dust; D007527:Isoenzymes; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon