Carbon Nanotubes and Crystalline Silica Stimulate Robust ROS Production, Inflammasome Activation, and IL-1Β Secretion in Macrophages to Induce Myofibroblast Transformation

Details

• Personal Author:
  Hindman B ; Ma Q
• Description:
  Pulmonary exposure to inhaled particulates elicits complex inflammatory and fibrotic responses that may progress to chronic fibrosis. The fibrogenic potentials of respirable particulates are influenced by their physicochemical properties and their interactions with major pathways to drive fibrotic development in the lung. Macrophages were exposed to six carbon nanotubes (CNTs) of varying dimensions, crystalline silica, or carbon black (CB), with lipopolysaccharide (LPS) and transforming growth factor (TGF)-beta1 as positive controls. Macrophage-conditioned media was collected and applied to cultures of human pulmonary fibroblast line WI(38)-VA(13) to induce myofibroblast transformation. Multi-walled and single-walled CNTs (MWCNTs and SWCNTs, respectively) and silica, but not CB, stimulated robust myofibroblast transformation through macrophage-conditioned media. On an equal weight basis, MWCNTs induced higher induction than SWCNTs. High induction was observed for MWCNTs with a long and slender or a short and rigid shape, and silica, at levels comparable to those by LPS and TGF-beta1. Fibrogenic particulates induced high levels of IL-1beta mRNA expression and protein secretion that are required for macrophage-guided myofibroblast transformation. Induction of IL-1beta is dependent on the activation of the NLRP(3) (NOD-like receptor family, pyrin domain containing 3) inflammasome and ROS (reactive oxygen species) production in macrophages, as inhibition of NLRP(3) by MCC(950) and reduction of ROS production by N-acetylcysteine blocked NLRP(3) activation, IL-1beta induction, and fibroblast activation and differentiation. Therefore, fibrogenic CNTs and silica, but not CB, elicit robust macrophage-guided myofibroblast transformation, which depends on the induction of IL-1beta through the NLRP(3) inflammasome pathway and the increased production of ROS in macrophages. [Description provided by NIOSH]
• Subjects:
  Blood Fibrosis Lung Lung Diseases Macrophages Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide Toxicology

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• Keywords:
  Author Keywords: Carbon Nanotube Carbon Black Carbon Nanotubes CNT Crystalline Silica Fibroblasts IL-1β Lung Disorders Macrophage Myofibroblast Nanomaterials Nanotoxicology NLRP3 Inflammasome Particulates Proteins ROS Silica

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• ISSN:
  0340-5761
• Document Type:
  Text
• Genre:
  Journal Article
• 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
• Volume:
  93
• Issue:
  4
• NIOSHTIC Number:
  nn:20055196
• Citation:
  Arch Toxicol 2019 Apr; 93(4):887-907
• Contact Point Address:
  Qiang Ma, 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, Morgantown, WV 26505
• Email:
  qam1@cdc.gov
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6) ; Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Archives of Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:97125369a1157a86dd9b2fcc4c43608440847197d5511d15d17cd5c685c01df7bdf4b53e065fc39fe46809e450003fdb2f3c4391c3263364487fa9f89c9dbcdc
• Download URL:
  https://stacks.cdc.gov/view/cdc/217553/cdc_217553_DS1.pdf
• File Type:
  [PDF - 7.52 MB ]