Mechanisms of toxicity induced by SiO2 nanoparticles of in vitro human alveolar barrier: effects on cytokine production, oxidative stress induction, surfactant proteins A mRNA expression and nanoparticles uptake

• Published in: Nanotoxicology 2013-09, Vol.7 (6), p.1095-1110
• Main Authors: Farcal, Lucian Romeo, Uboldi, Chiara, Mehn, Dora, Giudetti, Guido, Nativo, Paola, Ponti, Jessica, Gilliland, Douglas, Rossi, François, Bal-Price, Anna
• Format: Article
• Language: English
• Subjects: alveolar barrier; Biological and medical sciences; Cell Line; Cell Survival; Chemical and industrial products toxicology. Toxic occupational diseases; Cross-disciplinary physics: materials science; rheology; Cytokines - metabolism; Electric Impedance; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Exact sciences and technology; Humans; in vitro model; inflammation; Inorganic dusts (pneumoconiosises) and organic dusts (byssinosis etc.); Lipopolysaccharides; Macrophages - physiology; Materials science; Medical sciences; Monocytes - physiology; Nanoparticles - chemistry; Nanoparticles - toxicity; Nanoscale materials and structures: fabrication and characterization; Oxidative Stress - drug effects; Physics; Pulmonary Alveoli - drug effects; Pulmonary Surfactant-Associated Protein A - genetics; Pulmonary Surfactant-Associated Protein A - metabolism; Reactive Oxygen Species; RNA, Messenger - genetics; RNA, Messenger - metabolism; silica nanoparticles; Silicon Dioxide - chemistry; Silicon Dioxide - toxicity; toxicity mechanisms; Toxicology
• ISSN: 1743-5390; 1743-5404
• DOI: 10.3109/17435390.2012.710658

Abstract An in vitro human alveolar barrier established by the coculture of epithelial human cell line NCI-H441 with endothelial human cell line ISO-HAS1 was used to evaluate the effects of amorphous silicon dioxide nanoparticles (SiNPs), in the presence or absence of THP-1 cells (monocytes). SiNPs exposure induced production of proinflammatory cytokine and oxidative stress. A high release of TNF-α and IL-8 by epithelial/endothelial cells, potentiated in the presence of THP-1 cells could contribute to the observed downregulation of surfactant proteins A mRNA expression resulting in the damage of the alveolar barrier. The obtained results suggested that in vitro approach can be used to study pulmonary toxicity as long as the applied in vitro model mimics closely the complexity of in vivo situation.