Interferon signaling, systemic inflammation, and atherosclerosis following welding fume inhalation exposure: from the lung to the blood to the vasculature

Details

• Personal Author:
  Antonini JM ; Chen BT ; Erdely A ; Frazer DG ; Hulderman T ; Kashon ML ; Li S ; Liston AL ; Salmen-Muniz R ; Simeonova PP ; Stone S ; Zeidler-Erdely PC
• Description:
  Inhalation of particulates can result in measurable systemic markers related to adverse cardiovascular outcomes. Our aim was the determination of a systemic signature and atherosclerosis progression following gas metal arc-stainless steel (GMASS) welding fume exposure. C57BL/6 mice were exposed for 10d to GMA-SS by inhalation (40mg/m3 for 3hr/day) and harvested 4hr, 14d and 28d post-exposure. Systemic responses were measured by serum protein profiling and microarray (Ingenuity pathway analysis and real-time RT-PCR confirmation) for whole blood cells, aorta and lung. Atherosclerotic susceptible apolipoprotein E knockout (apoE- /-) mice were exposed (40mg/m3 for 3hr/day) during week 6 and 7 of two months of Western (high fat) diet feeding. Exposed C57BL/6 mice exhibited a specific network of type I interferon signaling in blood cells and aorta from 4hr to 28d post-exposure The central component of the network was the transcription factor interferon regulatory factor 7 (Irf7), the master regulator of the type I interferon response. Increases in related genes (Oasl2 and Ifitm3) were also validated. Type I interferon signaling was also a top network in the lung supporting the concept of a systemic signature reflecting the ongoing pulmonary response. Serum levels of primary inflammatory mediators were not elevated although oncostatin M, an IL-6 family cytokine and type I interferon enhancer, was increased. In apoE-/- mice, pulmonary inflammation, serum levels of IL-1â and MAC-3 and blood cell expression of Irf7 were increased post-GMA-SS exposure. Atherosclerosis severity, determined by plaque area and intensity in the aorta (en face), was increased. The data suggest an immunomodulatory and mild systemic inflammatory effect with increased progression of atherosclerosis due to GMA-SS exposure. Most notably, a pulmonary and corresponding systemic signature of type I interferon signaling was consistently evident across tissue and time. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Animals Cardiovascular Diseases Cardiovascular System Irritants Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Welding

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• Keywords:
  Animal-studies Cardiopulmonary-function Cardiopulmonary-system Cardiopulmonary-system-disorders Cardiovascular-function Cardiovascular-system-disorders Fumes Laboratory-animals Lung-disorders Lung-function Pulmonary-disorders Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiratory-irritants Respiratory-system-disorders

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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
• Pages in Document:
  39
• Volume:
  120
• NIOSHTIC Number:
  nn:20038426
• Citation:
  Toxicologist 2011 Mar; 120(Suppl 2):39
• Federal Fiscal Year:
  2011
• 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-512:544e87b3593be13d18e99193c4d3bd3161c2d5d04d9f58b408c3b48e66dbc45f8ac0b815b891e6b4f02aa351e32f0f65d93dbbd4f975cb45a7c4a131440c2999
• Download URL:
  https://stacks.cdc.gov/view/cdc/192140/cdc_192140_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]