title: Single-Walled Carbon Nanotubes Induce Fibrogenic Effect by Disturbing Mitochondrial Oxidative Stress and Activating NF-κB Signaling.
abstract: Single-walled carbon nanotubes (SWCNTs) are newly discovered material of crystalline carbon that forms single-carbon layer cylinders with nanometer diameters and varying lengths. Although SWCNTs are potentially suitable for a range of novel applications, their extremely small size, fiber-like shape, large surface area, and unique surface chemistry raise potential hazard to humans, including lung toxicity and fibrosis. The molecular mechanisms by which SWCNTs cause lung damage remain elusive. Here we show that SWCNTs dose and time-dependently caused toxicity in cultured human bronchial epithelial (BEAS-2B), alveolar epithelial (A549), and lung fibroblast (WI38) cells. At molecular levels, SWCNTs induced significant mitochondrial depolarization and ROS production at subtoxic doses. SWCNTs stimulated the secretion of proinflammatory cytokines and chemokines TNFα, IL-1β, IL-6, IL-10 and MCP1 from macrophages (Raw 264.7), which was attributed to the activation of the canonical signaling pathway of NF-κB by SWCNT. Finally, SWCNTs stimulated profibrogenic growth factors TGFβ1 production and fibroblast-to-myofibroblast-transformation. These results indicate that SWCNTs has a potential to induce human lung damage and fibrosis by damaging mitochondria, generating ROS, and stimulating production of proinflammatory and profibrogenic cytokines and growth factors.
authors.affiliation: Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division,National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, USA.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: He
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, USA.
authors.forename: Shih-Houng
authors.initials: SH
authors.lastname: Young
authors.affiliation: Chemical Exposure and Measuring Branch, Division of Applied Research and Technology, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Fernback
authors.affiliation: Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division,National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ma
keywords: Alveolar epithelial; Canonical signaling; Human bronchial epithelial; Single-walled carbon nanotubes