Silica nanoparticles induce endoplasmic reticulum stress response and activate mitogen activated kinase (MAPK) signalling.

Humans may be exposed to engineered silica nanoparticles (SiO-NPs) but potential adverse effects are poorly understood, in particular in relation to cellular effects and modes of action. Here we studied effects of SiO-NPs on cellular function in human hepatoma cells (Huh7). Exposure for 24 h to 10 and 50 μg/ml SiO-NPs led to induction of endoplasmic reticulum (ER) stress as demonstrated by transcriptional induction of , , , as well as CHOP target genes , , and . In addition, CHOP protein was induced. In addition, SiO-NPs induced an inflammatory response as demonstrated by induction of TNF-α and . Activation of MAPK signalling was investigated employing a PCR array upon exposure of Huh7 cells to SiO-NPs. Five of 84 analysed genes, including , , and exhibited significant transcriptional up-regulation, and 18 genes a significant down-regulation. Strongest down-regulation occurred for the proto-oncogene , , one of the four p38 MAPK genes, and for . Strong induction of , and was found after exposure to 50 μg/ml SiO-NPs for 24 h. To analyse for effects derived from up-regulation of TNF-α, Huh7 cells were exposed to SiO-NPs in the presence of the TNF-α inhibitor sauchinone, which reduced the induction of the transcript by about 50%. These data demonstrate that SiO-NPs induce ER stress, MAPK pathway and lead to inflammatory reaction in human hepatoma cells. Health implications of SiO-NPs exposure should further be investigated for a risk assessment of these frequently used nanoparticles.