Potential Roles of ROS and NF-kappaB in TNF-alpha Release in Rat Alveolar Macrophages Exposed to Single-Walled Carbon Nanotubes

The pulmonary toxicology of carbon nanotubes (CNTs) was highlighted recently when single-walled carbon nanotubes (SWCNTs) were reported to be highly toxic and fibrotic in mice and in rats when administered by intratracheal instillation. Therefore, it is necessary to evaluate the effects of SWCNTs on human health and the environment before utilizing them on a large scale. The purpose of this study was designed to assess the effects of SWCNTs on tumor necrosis factor-alpha (TNF-alpha) release and to elucidate possible molecular mechanisms in primary rat alveolar macrophages as a model system. Our results showed exposure of the cultured alveolar macrophages to SWCNTs elicited a concentration-dependent TNF-alpha release and reactive oxygen species (ROS) production in alveolar macrophages. In the presence of the antioxidants N-acetyl-Lcysteine (NAC) and glutathione (GSH), the SWCNTs-induced of TNF-alpha release and ROS production was significantly reduced. SWCNTs treatment caused an activation of the redox-sensitive transcription factor nuclear factor-kappaB (NF-kappaB). Pretreatment of alveolar macrophages with NF-KB inhibitors, L-l-tosylamido-2-phenylethyl chloromethyl ketone (TPCK) and parthenolide, suppressed SWCNTs-induced TNF-alpha expression. These results indicate that SWCNTs are able to induce TNF-alpha release in rat primary alveolar macrophages, at least in part, mediated by oxidative stress and NF-KB activation.