Proinflammatory responses and inflammasome activation by sintered indium-tin oxide particles

Details

• Personal Author:
  Badding MA ; Cummings, Kristin J. ; Fix NR ; Leonard, Stephen S.
• Description:
  Indium-tin oxide (ITO) is used to make transparent conductive coatings for touchscreen and liquid crystal display electronics. As the demand for consumer electronics continues to increase, so does the concern over occupational exposures to particles containing these potentially toxic metals. Epidemiologic studies have shown that workers exposed to ITO develop pulmonary alveolar proteinosis and fibrotic interstitial lung disease. Indium-containing compounds have been shown to be pro-inflammatory in animal models of indium lung disease, but how these particles initiate immune responses remains unknown. Our preliminary studies showed that sintered ITO (SITO) exposures caused significant cell death, NFkB activation, and cytokine production (IL-1B, IL-6, TNFalpha, and IL-8) within 24 h in RAW 264.7 macrophages and BEAS-2B bronchial epithelial cells, confirming pro-inflammatory responses. These results suggest NLRP3 inflammasome activation, which has been implicated in several immune-mediated diseases and pulmonary fibrosis via its ability to induce IL-1B release. This cytoplasmic, multi-protein complex responds to an array of different stressors but typically requires two signals. One involves toll-like receptor (TLR) priming through NFkB for the transcription of pro-IL-1B and the other activates caspase-1 for the processing and release of biologically-active IL-1B. When inflammasome components were blocked upstream or downstream of NLRP3, SITO-induced IL-1B production was significantly reduced. Further, SITO was able to cause significant caspase-1 activation. These results suggest that SITO particles were able to activate the inflammasome and subsequent cytokine production. Thus, it is possible that activation of the NLRP3 inflammasome by SITO plays a role in initiating and propagating indium lung disease. These findings will provide a better understanding of the mechanisms behind an emerging occupational health issue and will aid in the discovery of biomarkers for disease prevention. [Description provided by NIOSH]
• Subjects:
  Computers Environmental Monitoring Fibrosis Lung Lung Diseases Metals Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Exposure-assessment Fibrogenesis Fibrogenicity Lung-disease Lung-disorders Lung-fibrosis Metal-compounds Monitors Nanotechnology Respiratory-system-disorders
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; DRDS - Division of Respiratory Disease Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20046001
• Citation:
  Toxicologist 2015 Mar; 144(1):519
• CAS Registry Number:
  Indium tin oxide (In1.69Sn0.15O2.85) (CAS RN 71243-84-0)
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d9209cd3a87751998509d5272849c4a3cdd5ab0f5fe8477585cbdc198bc6866514d1f8841fcbc3c67da9b44152f6fc950401f249b276866ec945fa28d5ba6d96
• Download URL:
  https://stacks.cdc.gov/view/cdc/201199/cdc_201199_DS1.pdf
• File Type:
  [PDF - 221.96 KB ]