Silica-triggered Cellular Signaling without Immediate Increase of ROS in A549 Cells

Abstract

Silica has been known to be a factor in acute cell injury and chronic pulmonary fibrosis. To date, many studies have emphasized the reactive oxygen species (ROS) as a primary cause of this pathogenesis. Previously, we demonstrated that silica induced acute radical generation and intracellular Ca2+ increase in Rat2 cells. Moreover, increases in intracellular Ca2+ directly affect the rapid degradation of peroxiredoxin (Prx), a newly discovererd antioxidant enzyme family. In the present study, we investigated the mechanism by which silica transfers its cellular signal downstream of the cell by using human lung epithelial cells, which are known to contribute to the inflammatory response after exposure to silica in the lung. In A549 cells, silica induced the generation of ROS immediately, although immediate responses were observed in C6 cells or in Rat2 cells. Nevertheless, the immediate production of ROS in response to silica in A549 cells was not clearly detected, but the initial step for NF-κB signaling, such as rapid degradation of IκB-α, was sensitive to the addition of silica. Additionally, silica triggered the rapid degradation of cytoplasmic antioxidant enzymes such as PrxI and PrxII, indicating that this may accelerate silica-induced cellular damage. Moreover, silica was observed to increase intracellular Ca2+ concentration. This report suggests that silica transduces diverse pathways, such as the rapid increase of intracellular Ca2+ concentration, NF-κB signaling or modulation of redox potential by destruction of antioxidant enzymes, without the immediate generation of ROS in A549 cells.