Silica-Induced Pulmonary Inflammation in Rats: Activation of NF Kappa B and Its Supression by Dexamethasone

Details

• Personal Author:
  Bylander J ; Castranova, Vincent ; Gordon, Jane E. ; Kazmarczyk W ; Porter, Dale ; Reasor MJ ; Sacks M ; Shi XL ; Van Dyke K
• Description:
  Inhalation of silica is characterized by initial pulmonary inflammation leading to fibrosis. The goal of this study was to determine the relationship of the transcriptional regulatory factor, nuclear factor kappa B (NFkB) to the early inflammatory events involved with silica exposure. Male F-344 rats received an intratracheal of silica (2Omg/0.5ml) or saline. At 1, 3, 6 and 18 hours post-installation, the rats underwent broncheoalveolar lavage (BAL) for analysis of inflammation. From 3 hours post-instillation and onward, the silica-instilled (51) rats showed significant increases in BAL fluid neutrophil and lymphocyte counts as compared to the saline controls. BAL fluid cells from the 51 group also showed a significant increase in luminol-dependent chemiluminescence (LDCL) as compared to the controls. NFkB was present at 3 hours post- instillation and continued throughout the 18 hour time course. Dexamethasone (Dex) has been shown to inhibit NFkB expression invitro, but this has not been examined in the lung in-vivo. Treatment with Dex (5mg/kg) at - 3 and 0 hours prior to silica instillation and + 1.5 hour post instillation resulted in both a reduction in NFkB expression (by 70%) at 3 hours post-instillation as well as corresponding reductions in LDCL. BAL fluid cell count and BAL fluid inflammatory cells. These results show silica-induced pulmonary inflammation is associated with activation of NFkB and the inhibition of its activation correlates with suppression of inflammation. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Animals Fibrosis Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide

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• Keywords:
  Animal-studies Laboratory-animals Laboratory-testing Pulmonary-congestion Pulmonary-disorders Pulmonary-function Pulmonary-system Silica-dusts Silicates Silicosis
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 10 ; OSHA Region 3 ; Washington ; 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:
  42
• NIOSHTIC Number:
  nn:20025114
• Citation:
  Toxicologist 1998 Mar; 42(1-S):350
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  1998
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 37th Annual Meeting, March 1-5,1998, Seattle, Washington
• Supplement:
  1-S
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b108ef6b6f8e958ebbe86bff199b2c6e84da0e5b3d0feeb331635e4fd0c7201f07ec2e45c0bb7d21c1cc0d17cfbc140bd41e55317e9e88e043a01379d1da3d91
• Download URL:
  https://stacks.cdc.gov/view/cdc/196607/cdc_196607_DS1.pdf
• File Type:
  [PDF - 139.72 KB ]