Type I interferon and pattern recognition receptor signaling following particulate matter inhalation

Details

• Personal Author:
  Antonini JM ; Chen BT ; Erdely A ; Frazer DG ; Gu JK ; Hulderman T ; Kashon ML ; Li S ; Liston A ; Salmen-Muniz R ; Simeonova PP ; Stone S ; Zeidler-Erdely PC
• Description:
  Background: Welding, a process that generates an aerosol containing gases and metal-rich particulates, induces adverse physiological effects including inflammation, immunosuppression and cardiovascular dysfunction. This study utilized microarray technology and subsequent pathway analysis as an exploratory search for markers/mechanisms of in vivo systemic effects following inhalation. Mice were exposed by inhalation to gas metal arc - stainless steel (GMA-SS) welding fume at 40 mg/m3 for 3 hr/d for 10 d and sacrificed 4 hr, 14 d and 28 d post-exposure. Whole blood cells, aorta and lung were harvested for global gene expression analysis with subsequent Ingenuity Pathway Analysis and confirmatory qRT-PCR. Serum was collected for protein profiling. Results: The novel finding was a dominant type I interferon signaling network with the transcription factor Irf7 as a central component maintained through 28 d. Remarkably, these effects showed consistency across all tissues indicating a systemic type I interferon response that was complemented by changes in serum proteins (decreased MMP-9, CRP and increased VCAM1, oncostatin M, IP-10). In addition, pulmonary expression of interferon alpha and beta and Irf7 specific pattern recognition receptors (PRR) and signaling molecules (Ddx58, Ifih1, Dhx58, ISGF3) were induced, an effect that showed specificity when compared to other inflammatory exposures. Also, a canonical pathway indicated a coordinated response of multiple PRR and associated signaling molecules (Tlr7, Tlr2, Clec7a, Nlrp3, Myd88) to inhalation of GMA-SS. Conclusion: This methodological approach has the potential to identify consistent, prominent and/or novel pathways and provides insight into mechanisms that contribute to pulmonary and systemic effects following toxicant exposure. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Animals Biomarkers Cardiovascular Diseases Cardiovascular System Chromium Genetics Hazardous Substances Immune System Laboratories Metals Occupational Health Respiratory System Respiratory Tract Diseases Safety Welding

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• Keywords:
  Animal-studies Aorta Author Keywords: Microarray Biological-effects Biomarker Blood-serum Cardiopulmonary-function Cardiopulmonary-system Cardiopulmonary-system-disorders Cardiovascular-function Cardiovascular-system-disorders Cardiovascular Disease Cell-function Cellular-reactions Chromium-compounds Dose-response Fumes Gas-mixtures Genes Immune-reaction Immunotoxins In-vivo-study Inhalation Inhalation-studies Interferon Regulatory Factor 7 Laboratory-animals Metal-fumes Pattern Recognition Receptor Physiological-effects Proteins Stainless-steel Tissue-culture Toxic-dose Toxic-effects Whole Blood Cell Gene Expression

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• ISSN:
  1743-8977
• 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
• Pages in Document:
  25
• Volume:
  9
• NIOSHTIC Number:
  nn:20041641
• Citation:
  Part Fibre Toxicol 2012 Jul; 9:25
• Contact Point Address:
  Aaron Erdely, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA
• CAS Registry Number:
  Chromium (CAS RN 7440-47-3)
• Federal Fiscal Year:
  2012
• Peer Reviewed:
  True
• Source Full Name:
  Particle and Fibre Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:708dc37f96da20fa9291cfdb52549b0c209e568892868659387488df02c8c460d225c10c76ec0e25c8d2af49c409c24b490f3530db67bb2b5dd54e489bf64c25
• Download URL:
  https://stacks.cdc.gov/view/cdc/194143/cdc_194143_DS1.pdf
• File Type:
  [PDF - 1.40 MB ]