TGF-B1 mediated SWCNT induced lung fibrosis depends on the upstream osteopontin stimulation

Details

• Personal Author:
  Kagan V ; Khaliullin T ; Kisin E ; Murray A ; Shurin M ; Shvedova A ; Yanamala N
• Description:
  Several studies have demonstrated that single-walled carbon nanotubes (SWCNT) exposure caused pulmonary fibrosis with a rapid inflammatory onset and subsequent granulomas formation through mechanisms involving epithelial-mesenchymal transition, myofibroblast ROS-dependent differentiation/recruitment accompanied by the release and interplay of various cytokines/chemotactic factors. The transforming growth factor-beta (TGF-beta) has been recognized as a central player in the robust pulmonary inflammatory response involved in the development of granulomas and interstitial fibrosis. However, the role of glycoprotein osteopontin (OPN) in TGF-beta1 mediated fibrosis has not been fully explored. We used OPN-knockout (OPN-KO) and wild type (WT) C57BL/6 mice to investigate pulmonary fibrotic response upon exposure to SWCNT (40 microg/mouse). Reduced release of pro-inflammatory cytokines (MCP-1, TNF-beta, IL-6), diminished pulmonary damage markers, and less pronounced neutrophil accumulation were found in broncho-alveolar lavage (BAL) of OPN-KO mice as compared to WT mice. Morphological examination revealed markedly decreased formation of granulomatous lesions along with diminished collagen deposition in the lungs of OPN-KO mice. While a significant increase in the level of TGF-beta1 was found in BAL of WT mice, TGF-beta1 readings in OPN-KO animals remained unaltered. In line with this, significantly reduced levels of TGF-beta1 were detected when RAW 264.7 cells and MLE-15 cells exposed to SWCNT (24 hours, 6 microg/cm2 to 48 microg/cm2) were pre-treated with an OPN-blocking antibody. To the best of our knowledge, this is the first report to demonstrate that OPN may play a crucial role in TGF-beta1 mediated SWCNT induced lung fibrosis. Supported by grants NORA 933051G and FP7-NANOSOLUTIONS no. 309329. [Description provided by NIOSH]
• Subjects:
  Biomarkers Environmental Exposure Fibrosis Genetics Immune System Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Author Keywords: Carbon-based Nanomaterials Carbon Nanotubes Cell Biology Cell Function Cellular Function Cellular Reactions Cytokines Exposure Assessment Exposure Levels Fibroblasts Genes Glycoproteins Immune Reaction Immune System In Vitro Study In Vitro Toxicology In Vivo Study In Vivo Toxicology Laboratory Animals Laboratory Testing Lung Fibrosis Morphology Neutrophils Proteins Pulmonary Disorders Pulmonary Effects Pulmonary Fibrosis Pulmonary System Disorders Reactive Oxygen Species ROS Single-walled Carbon Nanotubes SWCNT

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• Publisher:
  International Nanotoxicology Congress
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Massachusetts ; OSHA Region 1 ; 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
• NIOSHTIC Number:
  nn:20048170
• Citation:
  nanoTOX 2016, Proceedings of the 8th International Nanotoxicology Congress, June 1-4, 2016, Boston, Massachusetts. Boston: MA: International Nanotoxicology Congress, 2016 Jun; :156
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  nanoTOX 2016, Proceedings of the 8th International Nanotoxicology Congress, June 1-4, 2016, Boston, Massachusetts
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b17438d36622999a3a48bdc413d4af107d453c5df9cd4a2c1c75d200754b7e8e0f1e3c0b0af386520e51adcff296061f3d8f201c1df9e7dd0b1439ce33804063
• Download URL:
  https://stacks.cdc.gov/view/cdc/202991/cdc_202991_DS1.pdf
• File Type:
  [PDF - 406.84 KB ]