Silicon dioxide nanoparticles induce COX-2 expression through activation of STAT3 signaling pathway in HaCaT cells.

Silicon dioxide nanoparticles (SiO-NPs) are widely used in biomedicines and consumer products, such as sunscreens and cosmetics. However, SiO-NPs can cause adverse effects on human health, depending on the size and concentration of nanoparticles. The present study was aimed at investigating the molecular mechanism underlying SiO-NPs-induced inflammation in human keratinocyte (HaCaT) cells. Incubation of HaCaT cells with SiO-NPs induced the expression of cyclooxygenase-2 (COX-2) mRNA and protein. Treatment of cells with SiO-NPs also induced the phosphorylation, DNA binding and the reporter gene activity of signal transducer and activator of transcription 3 (STAT3). Transfection of cells with STAT3 siRNA abrogated SiO-NPs-induced COX-2 expression. Moreover, SiO-NPs enhanced the phosphorylation of Janus kinase2 (JAK2), Src and Akt. Pharmacological inhibition of either JAK2, Src or Akt abrogated SiO-NPs-induced STAT3 transcriptional activity and the expression of COX-2. Treatment with LY294002 also attenuated SiO-NPs-induced Src phosphorylation, while, JAK2 phosphorylation was not changed. In addition, SiO-NPs generated reactive oxygen species (ROS) and treatment of N-acetyl cysteine (NAC) attenuated the phosphorylation of JAK2, Src, Akt and STAT3, as well as the expression of COX-2 in SiO-NPs-treated HaCaT cells. Taken together, our study provides the first report that SiO-NPs induce COX-2 expression in HaCaT cells by activating the STAT3 signaling through ROS-mediated phosphorylation of upstream kinases, Akt/Src and JAK2.