Molecular pathways of pulmonary inflammation following aspiration and inhalation of stainless steel welding fume in mice

Details

• Personal Author:
  Antonini J ; Erdely A ; Kashon M ; Li S ; Zeidler-Erdely PC
• Description:
  Previously, at comparable doses, we observed a greater inflammatory potency of inhaled versus aspirated gas metal arc-stainless steel (GMA-SS) welding fume in C57BL/6J (B6) mice. Also, aspiration of GMA-SS fume provoked a transient inflammation which resolved by 7d while inhalation resulted in a mounting response that remained unresolved at 28d post-exposure. Furthermore, we found by 28d after aspiration, lung gene expression was down-regulated which confirmed that inflammation was resolved. Here, we examined the lung transcriptional response after inhalation of GMA-SS fume and used gene network-based analysis to compare with previous aspiration data. Mice were exposed to GMA-SS fume at 40mg/m3 x 3hr/d for 10d. Necropsy was done at 28d after the last exposure and whole lung microarray was performed. A core analysis in IPA 8.7 was done on the inhalation data (p<0.05; fold change >1.5) followed by a core comparison analysis of the inhalation and aspiration datasets. We found that inhalation of GMA-SS welding fume was associated with activation of complement (C2, C3, C1QA-C, C4B), type 1 interferon pathways and increased expression of monocyte and lymphocyte chemotactic genes such as CCL2, CCL7 and CCL8. In addition, genes encoding the expression of molecules involved in T lymphocyte and natural killer cell regulation were increased (CD86 and CD69). Upon comparison of the datasets, a greater number of genes were changed with inhalation versus aspiration exposure. Involvement of IL1B as a central mediator to the lung response was apparent between the different exposure regimes as well as increased expression of MMP12. Transcriptional regulation of the lung response to GMA-SS aspiration involved FOS, EGR1, FOSB. In contrast, IRF7 and 9 as well as STAT1 and 2 were involved with inhalation. Overall, gene expression was reflective of the unresolved inflammation at 28d after inhalation of GMA-SS fumes. With the exception of a few molecules, differences in gene network signatures are apparent between aspiration and inhalation of GMASS welding fume in B6 mice. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Hazardous Substances Inhalation Exposure Irritants Laboratories Lung Occupational Health Respiratory Hypersensitivity Respiratory System Safety Welding

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• Keywords:
  Biological-effects Cell-biology Exposure-methods Fumes Gas-welders Inhalants Inhalation-studies Laboratory-animals Laboratory-testing Lung-cells Lung-function Lung-irritants Mathematical-models Molecular-biology Pulmonary-function Pulmonary-system Respiratory-gas-analysis Respiratory-hypersensitivity Respiratory-irritants Statistical-analysis Toxic-effects Welding-industry

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  District of Columbia ; 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:
  120
• NIOSHTIC Number:
  nn:20038647
• Citation:
  Toxicologist 2011 Mar; 120(Suppl 2):499
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC
• Supplement:
  2
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a41249d61b7ce4f2918b160e5eef8c151a9e2de8a59ce9ab4747f06658123b88d9da5b7a746a04aae4f1127c76a70829268600f26c0e5279274452dfcf8fbf9a
• Download URL:
  https://stacks.cdc.gov/view/cdc/192289/cdc_192289_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]