Single-walled carbon nanotubes induce fibrogenic effect by disturbing mitochondrial oxidative stress and activating NF-kB signaling.
He-X; Young-S-H; Fernback-JE; Ma-Q
J Clin Toxicol 2012 Jul; S5:005
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 TNFalpha, IL-1beta, IL-6, IL-10 and MCP1 from macrophages (Raw 264.7), which was attributed to the activation of the canonical signaling pathway of NF-kappaB by SWCNT. Finally, SWCNTs stimulated profibrogenic growth factors TGFbeta1 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.
Nanotechnology; Respiratory-irritants; Cytotoxicity; Cytotoxic-effects; Lung-cells; Lung-tissue; Alveolar-cells; Pulmonary-function; Lung-fibrosis; Health-hazards; Molecular-biology; Toxic-dose; Toxic-effects; Toxic-materials; Oxidation-reduction-reactions; Oxidative-processes; Fibrogenicity;
Author Keywords: Single-walled carbon nanotubes; Human bronchial epithelial; Alveolar epithelial; Canonical signaling
Xiaoqing He, Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Mailstop 3014, 1095 Willowdale Road, Morgantown, WV 26505, USA
Journal of Clinical Toxicology