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.
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-kappaB)/inhibitory kappa B (IkappaB) by Dunkerque city PM(2.5) in these target cells, by determination of phosphorylated p65 and phosphorylated IkappaBalpha 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-alpha 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-kappaB/IkappaB 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-kappaB/IkappaB complex preceded cytotoxicity in Dunkerque city PM-exposed L132 cells.
Dagher
Zeina
Z
LCE EA2598, Toxicologie Industrielle et Environnementale, Maison de la Recherche en Environnement Industriel de Dunkerque 2, 189A, Avenue Maurice Schumann, 59140 Dunkerque, France.
Garçon
Guillaume
G
Billet
Sylvain
S
Verdin
Anthony
A
Ledoux
Frédéric
F
Courcot
Dominique
D
Aboukais
Antoine
A
Shirali
Pirouz
P
D000397:Air Pollution / Q000032:analysis; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020672:I-kappa B Proteins / Q000737:chemistry / Q000378:metabolism; D008163:Luminescent Measurements; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D052638:Particulate Matter / Q000032:analysis / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606204:NFKBIA protein, human; D052638:Particulate Matter; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha