Submitted on April 3, 2007
Accepted on June 3, 2008
Arsenic upregulates MMP-9 and inhibits wound repair in human airway epithelial cells
Colin E. Olsen1, Andrew E. Liguori1, Yue Zong2, R. Clark Lantz3, Jefferey L. Burgess4, and Scott Boitano5*
1 Arizona Respiratory Center, Arizona Health Sciences Center, Tucson, Arizona, United States; Southwest Environmental Health Sciences Center, University of Arizona, Tucson, Arizona, United States
2 Arizona Respiratory Center, University of Arizona, Tucson, Arizona, United States
3 Cell Biology and Anatomy, Arizona Health Sciences Center, Tucson, Arizona, United States; Southwest Environmental Health Sciences Center, University of Arizona, Tucson, Arizona, United States; Bio5 Research Institute, University of Arizona, Tucson, Arizona, United States
4 Southwest Environmental Health Sciences Center, University of Arizona, Tucson, Arizona, United States; Mel & Enid Zuckerman College of Public Health, Arizona Health Sciences, Tucson, Arizona, United States
5 Arizona Respiratory Center, Arizona Health Sciences Center, Tucson, Arizona, United States; Southwest Environmental Health Sciences Center, University of Arizona, Tucson, Arizona, United States; Cell Biology and Anatomy, Arizona Health Sciences Center, Tucson, Arizona, United States; Bio5 Research Institute, University of Arizona, Tucson, Arizona, United States; Physiology, Arizona Health Sciences Center, Tucson, Arizona, United States
* To whom correspondence should be addressed. E-mail: sboitano{at}email.arizona.edu.
As part of the innate immune defense, the polarized conducting lung epithelium acts as a barrier to keep particulates carried in respiration from underlying tissue. Arsenic is a metalloid toxicant that can affect the lung via inhalation or ingestion. We have recently shown that chronic exposure of mice or humans to arsenic (10 - 50 ppb) in drinking water alters bronchiolar lavage or sputum proteins consistent with reduced epithelial cell migration and wound repair in the airway. In this report we used an in vitro model to examine effects of acute exposure of arsenic (15 - 290 ppb) on conducting airway lung epithelium. We found that arsenic at concentrations as low as 30 ppb and inhibits reformation of the epithelial monolayer following scrape wounds of monolayer cultures. In an effort to understand functional contributions to epithelial wound repair altered by arsenic, we showed that acute arsenic exposure increases activity and expression of MMP-9, an important protease in lung function. Further, inhibition of MMP-9 in arsenic treated cells improved wound repair. We propose that arsenic in the airway can alter the airway epithelial barrier by restricting proper wound repair in part through the upregulation of MMP-9 by lung epithelial cells.
