Suppression of basal and multi-walled carbon nanotube-induced lung inflammation and fibrosis by Nrf2

Details

• Personal Author:
  Dong J ; Ma Q
• Description:
  Exposure to multi-walled carbon nanotubes (MWCNT) has raised a concern regarding its potential health impact on humans, as certain forms of MWCNT induce prominent and rapid-onset lung inflammation and fibrosis in experimental animals. However, the molecular mechanisms by which MWCNT induce lung pathology remain largely unclear. Oxidative stress has been suggested as one of the major mechanisms of MWCNT toxicity, and the transcription factor Nrf2 serves as a critical regulator of the body's defense against oxidative stress. Therefore, in this study we determined whether Nrf2 functions in the occurrence and progression of inflammation and fibrosis in mouse lungs under basal and MWCNTchallenged conditions. In wild-type lungs, MWCNT exposure resulted in oxidative stress indicated by elevated levels of reactive oxygen species (ROS) production and oxidative stress indicators 8-0HdG, yH2AX and 4-HNE, activation of Nrf2 signaling, and up-regulation of Nrf2 target genes, such as the cytoprotective genes H0-1 and NQOl. In Nrf2 deficient lungs, remarkably higher levels of inflammation and fibrosis, as well as oxidative stress, were detected under both basal and MWCNTexposed conditions, than in wild-type lungs. These data reveal that oxidative stress promotes MWCNT-induced lung inflammation and fibrosis, and Nrf2 plays a protective function in this process. Meanwhile, Nrf2 has a basal activity and functions in maintaining lung homeostasis under physiological conditions. Our study provides a new mechanism for MWCNT-induced pathologic effects through reactive oxidants in the lungs, and offers direct evidence supporting the defense against oxidative stress, inflammation, and fibrosis in mouse lungs by Nrf2. [Description provided by NIOSH]
• Subjects:
  Animals Environmental Exposure Fibrosis Laboratories Lung Lung Diseases Occupational Health Oxygen Pathology Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Exposure Levels Health Effects Humans Laboratory Animals Lung Disorders Lung Fibrosis Molecular Biology Multi-walled Carbon Nanotubes MWCNT Oxidative Stress Risk Factors

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• Publisher:
  Keystone Symposia
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  66
• NIOSHTIC Number:
  nn:20048452
• Citation:
  Fibrosis: from basic mechanisms to targeted therapies joint with the meeting on stromal cells in immunity, Feb 7-11, 2016, Keystone, Colorado. Silverthorne, CO: Keystone Symposia, 2016 Feb; :66
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  Fibrosis: from basic mechanisms to targeted therapies joint with the meeting on stromal cells in immunity, Feb 7-11, 2016, Keystone, Colorado
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f39255b36fbc0b0ddbfadf717edd823c61d0c0d6142970cc67758869eaac831312602714cb9a9572c9ec331a367d59cdd723c89da9664e54832309555a694c70
• Download URL:
  https://stacks.cdc.gov/view/cdc/203203/cdc_203203_DS1.pdf
• File Type:
  [PDF - 879.89 KB ]