Single-Walled Carbon Nanotubes Induce Fibrogenic Effect by Disturbing Mitochondrial Oxidative Stress and Activating NF-ÃÂºB Signaling
1Receptor 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
3Chemical 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
- *Corresponding Author:
- Xiaoqing He
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, Mailstop 3014
1095 Willowdale Road, Morgantown, WV 26505, USA
Tel: 304 285-5990
Fax: 304 285-5708
Received date: March 26, 2012; Accepted date: July 13, 2012; Published date: July 17, 2012
Citation: He X, Young SH, Fernback JE, Ma Q (2012) Single-Walled Carbon Nanotubes Induce Fibrogenic Effect by Disturbing Mitochondrial Oxidative Stress and Activating NF-κB Signaling. J Clinic Toxicol S5:005. doi: 10.4172/2161-0495.S5-005
Copyright: © 2012 He X, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.