Multi-walled carbon nanotube-induced lung inflammation and fibrosis

Details

• Personal Author:
  Dong J ; Ma Q
• Description:
  Occupational and environmental exposure to respirable fibers and particles potentially causes lung fibrosis that is often progressive and non-curable in humans. The product ion of multi-walled carbon nanotubes (MWCNT) has been dramatically increased in recent years due to their widespread applications, which has raised a concern regarding their health impacts on humans. Considering the similarities of MWCNT and asbestos fibers. lung inflammation and fibrosis have been associated with the major pathologic effects of MWCNT. However, the features and molecular mechanisms of MWCNT-induced lung pathology are still largely unknown. We systematically studied the effects of pulmonary exposure to MWCNT on the initiation and progress ion of inflammation and fibrosis in mouse lungs. We found that MWCNT functioned as a potent fibrotic agent that induced rapid-onset and progressive fibrosis upon a single exposure to low doses; moreover, the fibrotic response was accompanied by significant in flammatory infiltration and cytokine expression that peaked before the appearance of marked fibrosis. To understand the underlying mechanism, we analyzed the effects of MWC T on the expression of a variety of pro-inflammatory, pro-fibrotic, and fibrosis marker genes at both mRNA and protein levels. Significan tly induced expression of these genes was observed in MWCNT-exposed mouse lungs and in partic ular, in the fib rotic foci where MWCNT were deposited, supporting that MWCNT trigger both inflammatory and fibro tic responses in the lungs. Furthermore, we found that Nrf2, a critical regulator of the body's defense to oxidative stress, played an important role in suppressing MWCNT-induced lung inflammation and fibrosis, evidenced by induced oxidative stress and activation ofNrf2 by MWCNT in wild type lungs, and remarkably enhanced levels of induced oxidative stress, inflammation and fibrosis observed in Nrf2 defi cient lungs upon MWCNT exposure. These findings reveal that MWCNT potently induce lung fibrosis that is preceded by an acute inflammatory response, and oxidative stress plays a role in this process. Our study provides a detailed evaluation on MWCNT-induced pathologic effects in the lungs, offers evidence on the utilization of MWCNT-treated mice as a new animal model to study lung fibrosis, and contributes to both the general concept on fibrogenesis and the mechanism identification specific to MWCNT-initiated fibrosis. [Description provided by NIOSH]
• Subjects:
  Animals Environmental Exposure Laboratories Lung Lung Diseases Men Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety Women

  More +
• Keywords:
  Environmental Exposure Fibrous Bodies Humans Laboratory Animals Lung Disease Lung Disorders Lung Fibrosis Lung Irritants Particulates Pulmonary Disorders Pulmonary Function Pulmonary System Pulmonary System Disorders Respiration Respiratory Irritants

  More +
• ISSN:
  2161-0495
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; 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:
  51
• Volume:
  5
• Issue:
  3
• NIOSHTIC Number:
  nn:20046735
• Citation:
  J Clin Toxicol 2015 Aug; 5(3):51
• Contact Point Address:
  Jie Dong, National Institute for Occupational Safety and Health, USA
• Email:
  wyo6@cdc.gov
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4)
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  Journal of Clinical Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f62b3e8b0e5a631b7553c90a6056d5a7abade92266530abb9180fa497f2487f18bacbfad334baf98b269768c879201b1882c996775308ae4ebe9ca212574c22a
• Download URL:
  https://stacks.cdc.gov/view/cdc/202069/cdc_202069_DS1.pdf
• File Type:
  [PDF - 558.26 KB ]