Concentration-dependent cytokine responses of silica nanoparticles and role of ROS in human lung epithelial cells.

Reactive oxygen species (ROS) is regarded as a critical denominator in nanoparticle toxicology and inflammation. Previously, we have shown that silica nanoparticles sized 50 nm (Si50) induce release of CXCL8 and IL-6 from BEAS-2B cells, via mechanisms involving NFκB, p38 MAPkinase, and TGF-α-activated EGF-receptor. In the present study, the role of ROS-mediated mechanisms in the concentration-dependent Si50-induction of CXCL8 and IL-6 responses was examined. Si50 (200 μg/ml) induced a time-dependent ROS formation, and a postponed increase in expression of heme oxygenase (HO-1) mRNA and protein. Pre-treatment with the ROS-inhibitors N-acetyl cysteine (NAC) and diphenyleneiodonium (DPI) partially attenuated CXCL8 and IL-6 responses to 200 μg/ml, but not to 100 μg/ml Si50. The release of TGF-α induced by Si50 (200 μg/ml) was significantly reduced by NAC, but not by DPI and siRNA against NADPH-oxidase DUOX-1 (siDUOX-1). Furthermore, siDUOX-1 reduced Si50-induced CXCL8, but not IL-6. Both p38- and p65-phosphorylations were inhibited by siDUOX-1, but for NAC only p65-phosphorylation reached a significant reduction. Neither NAC nor DPI reduced Si50-induced CXCL8 and IL-6 gene expressions. In conclusion, Si50 -induced CXCL8 and IL-6 involved both ROS-dependent and -independent mechanisms. Notably, the role of ROS seemed restricted to effects of higher concentrations of Si50 and not mediated via the gene expression. This article is protected by copyright. All rights reserved.