HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/L293    most recent 00134.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Olsen, C. E. Articles by Boitano, S. Search for Related Content PubMed PubMed Citation Articles by Olsen, C. E. Articles by Boitano, S.

Arsenic upregulates MMP-9 and inhibits wound repair in human airway epithelial cells

¹Arizona Respiratory Center; ²Southwest Environmental Health Sciences Center; ³Department of Cell Biology and Anatomy, School of Medicine; ⁴Bio5 Research Institute; ⁵Mel and Enid Zuckerman College of Public Health; and ⁶Department of Physiology, School of Medicine, Arizona Health Sciences Center, Tucson, Arizona

Submitted 3 April 2007 ; accepted in final form 3 June 2008

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 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 matrix metalloproteinase (MMP)-9, an important protease in lung function. Furthermore, 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.

sodium arsenite; matrix metalloproteinase; cell migration; 16HBE14o- cells; airway epithelial barrier