Role of nuclear factor-kappa B activation in the adverse effects induced by air pollution particulate matter (PM2.5) in human epithelial lung cells (L132) in culture

✍ Scribed by Zeina Dagher; Guillaume Garçon; Sylvain Billet; Anthony Verdin; Frédéric Ledoux; Dominique Courcot; Antoine Aboukais; Pirouz Shirali

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 212 KB
• Volume: 27
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.1211

✦ Synopsis

Abstract

ABSTRACT: To contribute to improving knowledge on the adverse health effects induced by particulate matter (PM) air pollution, an extensive investigation was undertaken of the underlying mechanisms of action activated by PM~2.5~ air pollution collected in Dunkerque, a strongly industrialized French seaside city. Their chemical and physical characteristics have been previously determined, and earlier in vitro short‐term studies have shown them to cause dose‐dependent and time‐dependent oxidative damage, gene expression and protein secretion of inflammatory mediators, and apoptotic events in human lung epithelial cells (L132) in culture. Hence, this work studied the activation of nuclear factor‐kappa B (NF‐κ__B)/inhibitory kappa B (I__κ__B) by Dunkerque city PM~2.5~ in these target cells, by determination of phosphorylated p65 and phosphorylated I__κ__B__α protein levels in cytoplasmic extracts, and p65 and p50 DNA binding in nuclear extracts. In PM‐exposed L132 cells, there were concentration‐ and/or time‐dependent increases in nuclear p65 and cytoplasmic IkB‐α phosphorylation, and nuclear p65 and p50 DNA binding. Taken together, these results showed that Dunkerque city PM~2.5~ were involved in the activation of the NF‐__κ__B/I__κ__B complex, notably through the occurrence of oxidative stress conditions, and, therefore, in the gene expression and protein secretion of inflammatory mediators in target L132 cells. Hence, these findings suggested that the activation of the NF‐__κ__B/I__κ__B complex preceded cytotoxicity in Dunkerque city PM‐exposed L132 cells. Copyright © 2007 John Wiley & Sons, Ltd.