Multi-walled carbon nanotubes induce proinflammatory cytokine expression by activating NF-kB signaling in mouse lungs

Details

• Personal Author:
  Dong J ; MaQ
• Description:
  Occupational and environmental exposure to respirable particles and fibers potentially causes lung fibrosis that is often progressive and non-curable in humans. The mechanism by which fibrogenic particulates and fibers induce pulmonary fibrosis is largely unknown. Multi-walled carbon nanotubes (MWCNT) are fiber-like, new materials of graphitic carbon with diameters in the nanometer range, and variable aspect ratios and surface chemistry, which render unique electronic, mechanical, and chemical properties. The health risk that MWCNT may impose on humans is unclear. MWCNT induce rapid-onset and progressive fibrosis in mouse lungs that is accompanied by significant inflammatory infiltration and cytokine expression. In this study, induction of gene expression was exploited to uncover the signaling pathways governing the inflammatory and fibrotic responses to MWCNT. MWCNT stimulated macrophages to transcribe and secrete proinflammatory cytokines including IL-1b, TNFa, IL-6, and MCP1. Moreover, MWCNT activated the NF-kB signaling pathway both in vivo and in cultured macrophages, evidenced by MWCNT-induced degradation of IkBa, nuclear accumulation of NF-kB p65, and binding of activated NF-kB to a consensus NF-kB DNA binding sequence. MWCNT stimulated the expression of a reporter gene under the control of either 5 copies of a NF-kB binding sequence or the mouse TNFa gene promoter that contains multiple copies of the NF-kB binding elements. Lastly, the culture media of macrophages exposed to MWCNT were found capable of activating fibroblasts to transform into myofibroblasts. Current studies are undertaken to elucidate the molecular events by which MWCNT trigger NF-kB activation. [Description provided by NIOSH]
• Subjects:
  Animals Chemistry Dust Environmental Exposure Fibrosis Irritants Laboratories Lung Lung Diseases Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Chemical-properties Environmental-exposure Exposure-levels Fibrous-dusts Laboratory-animals Mechanical-properties Molecular-biology Molecular-structure Nanotechnology Particulates Pulmonary-disorders Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiration Respiratory-irritants Respiratory-system-disorders 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:
  97
• NIOSHTIC Number:
  nn:20045680
• Citation:
  Fibrosis: From Bench to Bedside, Proceedings of the Keystone Symposia on Molecular and Cellular Biology, March 23-28, 2014, Keystone, Colorado. Silverthorne, CO: Keystone Symposia, 2014 Mar; :97
• Contact Point Address:
  Qiang Ma, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  Fibrosis: From Bench to Bedside, Proceedings of the Keystone Symposia on Molecular and Cellular Biology, March 23-28, 2014, Keystone, Colorado
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fd73f9751c056b254eb7c6a33b6dbfbd1a25bec432d97cc9ab4562f6ba03284f0b5122513e204b30aef8650106b399ee3dbcd2e3faf903ff0685fa2ab627ca79
• Download URL:
  https://stacks.cdc.gov/view/cdc/201011/cdc_201011_DS1.pdf
• File Type:
  [PDF - 1.06 MB ]