Synergistic Effect of WTC-Particulate Matter and Lysophosphatidic Acid Exposure and the Role of RAGE: In-Vitro and Translational Assessment

Details

• Personal Author:
  Caraher EJ ; Crowley G ; Haider SH ; Kwon S ; Lam R ; Liu M ; Nolan A ; Ostrofsky DF ; Prezant DJ ; Talusan A ; Wang Y
• Description:
  World Trade Center particulate matter (WTC-PM)-exposed firefighters with metabolic syndrome (MetSyn) have a higher risk of WTC lung injury (WTC-LI). Since macrophages are crucial innate pulmonary mediators, we investigated WTC-PM/lysophosphatidic acid (LPA) co-exposure in macrophages. LPA, a low-density lipoprotein metabolite, is a ligand of the advanced glycation end-products receptor (AGER or RAGE). LPA and RAGE are biomarkers of WTC-LI. Human and murine macrophages were exposed to WTC-PM, and/or LPA, and compared to controls. Supernatants were assessed for cytokines/chemokines; cell lysate immunoblots were assessed for signaling intermediates after 24 h. To explore the translatability of our in-vitro findings, we assessed serum cytokines/chemokines and metabolites of symptomatic, never-smoking WTC-exposed firefighters. Agglomerative hierarchical clustering identified phenotypes of WTC-PM-induced inflammation. WTC-PM induced GM-CSF, IL-8, IL-10, and MCP-1 in THP-1-derived macrophages and induced IL-1a, IL-10, TNF-a, and NF-kB in RAW264.7 murine macrophage-like cells. Co-exposure induced synergistic elaboration of IL-10 and MCP-1 in THP-1-derived macrophages. Similarly, co-exposure synergistically induced IL-10 in murine macrophages. Synergistic effects were seen in the context of a downregulation of NF-kB, p-Akt, -STAT3, and -STAT5b. RAGE expression after co-exposure increased in murine macrophages compared to controls. In our integrated analysis, the human cytokine/chemokine biomarker profile of WTC-LI was associated with discriminatory metabolites (fatty acids, sphingolipids, and amino acids). LPA synergistically elaborated WTC-PM's inflammatory effects in vitro and was partly RAGE-mediated. Further research will focus on the intersection of MetSyn/PM exposure. [Description provided by NIOSH]
• Subjects:
  Biomarkers Firefighters Lung Lung Diseases Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety September 11 Terrorist Attacks
• Keywords:
  Author Keywords: Lysophosphatidic Acid Cytokines Exposure Assessment Fire Fighters Lung Disorders Particulate Matter Exposure Particulates Pulmonary Effects Pulmonary Function RAGE Synergy World Trade Center WTC

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• ISSN:
  1660-4601
• Document Type:
  Text
• Funding:
  Cooperative Agreement ; Contract
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  17
• Issue:
  12
• NIOSHTIC Number:
  nn:20060058
• Citation:
  Int J Environ Res Public Health 2020 Jul; 17(12):4318
• Contact Point Address:
  Anna Nolan, Division of Pulmonary, Department of Medicine, Critical Care and Sleep Medicine, New York University (NYU) School of Medicine, New York, NY 10016, USA
• Email:
  anna.nolan@med.nyu.edu
• Federal Fiscal Year:
  2020
• Performing Organization:
  New York University School of Medicine
• Peer Reviewed:
  True
• Start Date:
  20170701
• Source Full Name:
  International Journal of Environmental Research and Public Health
• End Date:
  20260630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:16cf1ec7a5326f75f700fc703f25a26a6566b8e0ac2a0370c0550160080e518e63f6b99a15113797a8519b05158d14388c626e7ccf678d59f23dc3dd8628b343
• Download URL:
  https://stacks.cdc.gov/view/cdc/224091/cdc_224091_DS1.pdf
• File Type:
  [PDF - 663.61 KB ]