Open AccessSingle-Walled Carbon Nanotubes Induce Fibrogenic Effect by Disturbing Mitochondrial Oxidative Stress and Activating NF-κB Signaling
Author(s) -
Xiaoqing He,
ShihHoung Young,
Joseph E. Fernback,
Qiang Ma
Publication year - 2012
Publication title -
journal of clinical toxicology
Language(s) - English
Resource type - Journals
ISSN - 2161-0495
DOI - 10.4172/2161-0495.s5-005
Subject(s) - proinflammatory cytokine , myofibroblast , fibroblast , oxidative stress , microbiology and biotechnology , materials science , chemokine , carbon nanotube , nanotoxicology , pulmonary fibrosis , a549 cell , fibrosis , chemistry , biophysics , nanotechnology , inflammation , biology , cell , immunology , biochemistry , medicine , in vitro , pathology , nanoparticle
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.