ENVIRONMENTALLY PERSISTENT FREE RADICAL EXPOSURE CAUSES EPITHELIAL TO MESENCHYME TRANSITION IN HUMAN BRONCHIAL EPITHELIAL CELLS
Document Type
Presentation
Start Date
22-10-2010 10:45 AM
End Date
22-10-2010 12:00 PM
Description
Environmentally persistent free radicals (EPFRs) stabilized onto ultrafine particulate matter (<0.2μm) are the product of combustion and other thermal remediation processes. Despite numerous epidemiological studies linking particulate matter exposure to pathological conditions, little is known about the direct health effects of this ubiquitous subset of combustion generated pollution. Previous studies in our lab using a surrogate particle capable of producing, and regenerating, EPFRs (DCB230) have shown moderate cell toxicity in vitro along with negative lung function changes in vivo. These changes were associated with multiple indicators of oxidative stress including elevated levels of glutathione and 8-isoprostanes. The purpose of this study was to determine the specific cellular processes responsible for the pathological response due to DCB230. exposure in human bronchial epithelial cells. After exposure to DCB230, cells underwent an epithelial to mesenchyme transition (EMT) as evidenced by a loss of cell-cell adhesions and contraction from the confluent monolayer. The cobblestone morphology, typical of an epithelial cell, was lost in favor of a more "spindly" fibroblastic phenotype. Validating the phenotypic transition, we observed changes in protein expression consistent with EMT. These changes included a decrease in expression of E-cadherin, and an increase in expression of alpha smooth muscle actin, phosphorylated focal adhesion kinase, and collagen I deposition. Elevations in production of the pro-fibrotic cytokine transforming growth factor ~ were also observed. These results demonstrate, for the first time, a link between EPFR exposure and airway remodeling -a significant component of in the progression of chronic airway diseases such as asthma and chronic obstructive pulmonary disease.
Recommended Citation
Saravia, Jordy; Thevenot, P.; Giaimo, J.; and Cormier, S. A., "ENVIRONMENTALLY PERSISTENT FREE RADICAL EXPOSURE CAUSES EPITHELIAL TO MESENCHYME TRANSITION IN HUMAN BRONCHIAL EPITHELIAL CELLS" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 21.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/poster1/21
ENVIRONMENTALLY PERSISTENT FREE RADICAL EXPOSURE CAUSES EPITHELIAL TO MESENCHYME TRANSITION IN HUMAN BRONCHIAL EPITHELIAL CELLS
Environmentally persistent free radicals (EPFRs) stabilized onto ultrafine particulate matter (<0.2μm) are the product of combustion and other thermal remediation processes. Despite numerous epidemiological studies linking particulate matter exposure to pathological conditions, little is known about the direct health effects of this ubiquitous subset of combustion generated pollution. Previous studies in our lab using a surrogate particle capable of producing, and regenerating, EPFRs (DCB230) have shown moderate cell toxicity in vitro along with negative lung function changes in vivo. These changes were associated with multiple indicators of oxidative stress including elevated levels of glutathione and 8-isoprostanes. The purpose of this study was to determine the specific cellular processes responsible for the pathological response due to DCB230. exposure in human bronchial epithelial cells. After exposure to DCB230, cells underwent an epithelial to mesenchyme transition (EMT) as evidenced by a loss of cell-cell adhesions and contraction from the confluent monolayer. The cobblestone morphology, typical of an epithelial cell, was lost in favor of a more "spindly" fibroblastic phenotype. Validating the phenotypic transition, we observed changes in protein expression consistent with EMT. These changes included a decrease in expression of E-cadherin, and an increase in expression of alpha smooth muscle actin, phosphorylated focal adhesion kinase, and collagen I deposition. Elevations in production of the pro-fibrotic cytokine transforming growth factor ~ were also observed. These results demonstrate, for the first time, a link between EPFR exposure and airway remodeling -a significant component of in the progression of chronic airway diseases such as asthma and chronic obstructive pulmonary disease.