Title: Genetic determinants of susceptibility to silver nanoparticle-induced acute lung inflammation in mice.
Authors: Scoville, David K; Botta, Dianne; Galdanes, Karen; Schmuck, Stefanie C; White, Collin C; Stapleton, Patricia L; Bammler, Theo K; MacDonald, James W; Altemeier, William A; Hernandez, Michelle; Kleeberger, Steven R; Chen, Lung-Chi; Gordon, Terry; Kavanagh, Terrance J
Published In FASEB J, (2017 10)
Abstract: Silver nanoparticles (AgNPs) are employed in a variety of consumer products; however, in vivo rodent studies indicate that AgNPs can cause lung inflammation and toxicity in a strain- and particle type-dependent manner, but mechanisms of susceptibility remain unclear. The aim of this study was to assess the variation in AgNP-induced lung inflammation and toxicity across multiple inbred mouse strains and to use genome-wide association (GWA) mapping to identify potential candidate susceptibility genes. Mice received doses of 0.25 mg/kg of either 20-nm citrate-coated AgNPs or citrate buffer using oropharyngeal aspiration. Neutrophils in bronchoalveolar lavage fluid (BALF) served as markers of inflammation. We found significant strain- and treatment-dependent variation in neutrophils in BALF. GWA mapping identified 10 significant single-nucleotide polymorphisms (false discovery rate, 15%) in 4 quantitative trait loci on mouse chromosomes 1, 4, 15, and 18, and Nedd4l (neural precursor cell expressed developmentally downregulated gene 4-like; chromosome 18), Ano6 (anocatmin 6; chromosome 15), and Rnf220 (Ring finger protein 220; chromosome 4) were considered candidate genes. Quantitative RT-PCR revealed significant inverse associations between mRNA levels of these genes and neutrophil influx. Nedd4l, Ano6, and Rnf220 are candidate susceptibility genes for AgNP-induced lung inflammation that warrant additional exploration in future studies.-Scoville, D. K., Botta, D., Galdanes, K., Schmuck, S. C., White, C. C., Stapleton, P. L., Bammler, T. K., MacDonald, J. W., Altemeier, W. A., Hernandez, M., Kleeberger, S. R., Chen, L.-C., Gordon, T., Kavanagh, T. J. Genetic determinants of susceptibility to silver nanoparticle-induced acute lung inflammation in mice.
PubMed ID: 28716969
MeSH Terms: Animals; Bronchoalveolar Lavage Fluid/cytology*; Disease Susceptibility/metabolism*; Genome-Wide Association Study/methods; Lung/metabolism; Macrophages/drug effects; Macrophages/metabolism; Metal Nanoparticles/toxicity*; Mice; Neutrophils/drug effects*; Neutrophils/metabolism; Pneumonia/chemically induced; Pneumonia/genetics*; Polymorphism, Single Nucleotide/genetics; Silver