Single-walled carbon nanotubes induce fibrogenic effect by disturbing mitochondrial oxidative stress and activating NF-kB signaling

Details

• Personal Author:
  Fernback, Joseph E. ; He X ; Ma Q ; Young S-H
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Cytotoxins Hazardous Substances Lung Lung Diseases Occupational Health Oxidants Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Alveolar Cells Alveolar Epithelial Author Keywords: Single-walled Carbon Nanotubes Canonical Signaling Cytotoxic Effects Cytotoxicity Fibrogenicity Health Hazards Human Bronchial Epithelial Lung Cells Lung Fibrosis Lung Tissue Molecular Biology Nanotechnology Oxidation Reduction Reactions Oxidative Processes Pulmonary Function Respiratory Irritants Toxic Dose Toxic Effects Toxic Materials

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• ISSN:
  2161-0495
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; DART - Division of Applied Research and Technology
• Topic:
  Workplace Safety & Health
• Location:
  North America
• NIOSHTIC Number:
  nn:20041261
• Citation:
  J Clin Toxicol 2012 Jul; S5:005
• Contact Point Address:
  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
• Email:
  xah4@cdc.gov
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Clinical Toxicology
• Supplement:
  S5
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5c3c2a9286c8fe03e1b6f9539685b7d212e6d6a1819b927276fa12b40e4d56fbadd3ef4c082dab406b3b7de97d96e606cc5096ffd5e2a883beb9c54b9b5cf508
• Download URL:
  https://stacks.cdc.gov/view/cdc/193866/cdc_193866_DS1.pdf
• File Type:
  [PDF - 2.76 MB ]