Inflammasome formation and IL-1β release by human blood monocytes in response to silver nanoparticles

Abstract

In this study, the immunological effect of silver nanoparticles on innate immunity was investigated using primary human monocytes. After exposure to silver nanoparticles, production of IL-1β, a critical cytokine involved in induction of innate immunity, significantly increased as particle size decreased. These results suggest that silver nanoparticles may evoke an immunologically active state. The size effect of silver nanoparticles on IL-1β production was also further investigated. 5 nm and 28 nm silver nanoparticles induced inflammasome formation and subsequent caspase-1 activation. Using inhibitors, we found exposure to silver nanoparticles caused leakage of cathepsins from lysosomes and efflux of intracellular K(+). These two events induced superoxide within mitochondrial membranes, leading to inflammasome formation. 5 nm silver nanoparticles produced more hydrogen peroxide and were more cytotoxic than 28 nm silver nanoparticles, suggesting the balance between superoxide and hydrogen peroxide governs cell fate, death or activation. Moreover, these findings also suggest that the immunological significance of silver nanoparticles should be considered with respect to their capacity to synergistically activate immune responses.