Arsenic upregulates MMP-9 and inhibits wound repair in human airway epithelial cells.
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.
Arizona Respiratory Center, Arizona Health Sciences Center, 1501 N. Campbell Ave., Tucson, AZ 85724-5030, USA.
Colin E
CE
Olsen
Andrew E
AE
Liguori
Yue
Y
Zong
R Clark
RC
Lantz
Jefferey L
JL
Burgess
Scott
S
Boitano
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D015824:Blood-Air Barrier / Q000201:enzymology / Q000473:pathology; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects; D004847:Epithelial Cells / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051379:Mice; D010101:Oxygen Consumption / Q000187:drug effects; D020545:Respiratory Mucosa / Q000201:enzymology* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014945:Wound Healing / Q000187:drug effects*
D014874:Water Pollutants, Chemical; D020780:Matrix Metalloproteinase 9; D001151:Arsenic