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S97 Alveolar epithelial DNA damage, inflammation and altered autophagy following exposure to silver nanoparticles is exacerbated by viral ligands in vitro
  1. MZ Zambianchi,
  2. TD Tetley,
  3. AJ Thorley
  1. Imperial College, London, England

Abstract

Rationale Over the past decade there has been a rapid increase in the development and use of engineered nanoparticles. Silver (Ag) is the most commercialised nanomaterial in the world. Due to its antibacterial activity it is incorporated into a variety of consumer goods including silver nanoparticle sprays to treat pulmonary infection. However, little is known about silver nanoparticle (AgNPs) toxicity in the lung. We hypothesise that inhalation of AgNPs will trigger a pro-inflammatory response in the alveolar epithelium, which, in the presence of viral infection, will synergise with the innate immune response, leading to increased pulmonary epithelial inflammation, DNA damage and autophagy activation.

Methods Transformed human alveolar epithelial type-1-like cells (TT1) were exposed to AgNPs alone and in combination with Poly I:C, a synthetic analogue of double strand RNA that mimics viral infection. Oxidative stress level was measured by dihydroethidium staining. Levels of IL-6 and IL-8 were assessed by ELISA. DNA damage and autophagy marker LC3II/LC3I ratio were measured by western blot.

Results AgNPs induced oxidative stress in TT1 cells leading to enhanced inflammation, DNA double strand breakage and autophagy activation. The combination of Ag and Poly I:C potentiated IL-6 release (4-fold; p < 0.01) and DNA damage (3-fold; p < 0.01). Autophagy flux, activated by AgNPs alone, was slowed down by combined AgNPs and Poly I:C exposure.

Conclusion This study shows that Ag could induce oxidative stress in the lung, leading to a strong pro-inflammatory response and DNA damage, both potentiated by co-exposure to Poly I:C. Also, defective autophagy might result in certain human diseases such as cancer and neurodegenerative disease. This suggests that inhalation of AgNPs may have adverse health effects on the lung, that might be exacerbated by viral infection.

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