PT - JOURNAL ARTICLE AU - Martina Zambianchi AU - Andrew Thorley AU - Teresa Tetley TI - Induction of inflammation, oxidative stress and autophagy in human alveolar type I epithelial cells following exposure to silver nanoparticles DP - 2012 Sep 01 TA - European Respiratory Journal PG - P3707 VI - 40 IP - Suppl 56 4099 - http://erj.ersjournals.com/content/40/Suppl_56/P3707.short 4100 - http://erj.ersjournals.com/content/40/Suppl_56/P3707.full SO - Eur Respir J2012 Sep 01; 40 AB - The use of silver nanoparticles (AgNP) in health products is increasing due to their antimicrobial activity. However, their impact on health is poorly understood. It is known that the particle reactivity increases as size decreases, thus AgNPs may induce inflammatory responses that their bulk sized counterparts do not. It is known that 50% of inhaled nano-sized (<100nm) particles preferentially deposit in the peripheral lung. Thus, inhalation of AgNPs might have adverse effects on the alveolar epithelium. We hypothesize that AgNPs induce an oxidative stress-dependent proinflammatory response in the human alveolar epithelium and activate autophagy.Human alveolar type I epithelial cells (TT1) were exposed to 80nm AgNPs for up to 24h. IL-6 and IL-8 release was measured by ELISA and reactive oxygen species (ROS) production measured by dihydroethidium staining. n-acetylcysteine (NAC) was used to evaluate the role of ROS in mediator release. The plasmid assay was used to assess free radical-induced DNA damage and the autophagy markers LC3II/LC3I measured by immunoblotting.AgNPs induced significant oxidative stress within 4h and IL-6 and IL-8 by 24h. NAC pre-treatment inhibited Ag50μg/ml-stimulation of IL-6 by 60% (P<0.001). AgNPs induced significant DNA damage (density of supercoiled fraction: Ag1μg/ml=0.31; Ag50μg/ml=0.073) and induced a significant increase in the LC3II/LC3I ratio (P<0.01; Ag 50% vs nt), suggesting that AgNPs activate autophagy.Our study shows that AgNPs induce oxidative stress-dependent inflammation, DNA damage and a unique finding of autophagy responses in TT1 cells suggesting that AgNPs may have adverse effects on the lung.