Comparative Analysis of Lung and Blood Transcriptomes in Mice Exposed to Multi-Walled Carbon Nanotubes

Details

• Personal Author:
  Fatkhutdinova LM ; Khaliullin TO ; Kisin ER ; Newman MS ; Shvedova AA ; Yanamala N
• Description:
  Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) causes inflammation, fibroproliferation, immunotoxicity, and systemic responses in rodents. However, the search for representative biomarkers of exposure is an ongoing endeavor. Whole blood gene expression profiling is a promising new approach for the identification of novel disease biomarkers. We asked if the whole blood transcriptome reflects pathology-specific changes in lung gene expression caused by MWCNT. To answer this question, we performed mRNA sequencing analysis of the whole blood and lung in mice administered MWCNT or vehicle solution via pharyngeal aspiration and sacrificed 56 days later. The pattern of lung mRNA expression as determined using Ingenuity Pathway Analysis (IPA) was indicative of continued inflammation, immune cell trafficking, phagocytosis, and adaptive immune responses. Simultaneously, innate immunity-related transcripts (Plunc, Bpifb1, Reg3g) and cancer-related pathways were downregulated. IPA analysis of the differentially expressed genes in the whole blood suggested increased hematopoiesis, predicted activation of cancer/tumor development pathways, and atopy. There were several common upregulated genes between whole blood and lungs, important for adaptive immune responses: Cxcr1, Cd72, Sharpin, and Slc11a1. Trim24, important for TH2 cell effector function, was downregulated in both datasets. Hla-dqa1 mRNA was upregulated in the lungs and downregulated in the blood, as was Lilrb4, which controls the reactivity of immune response. "Cancer" disease category had opposing activation status in the two datasets, while the only commonality was "Hypersensitivity". Transcriptome changes occurring in the lungs did not produce a completely replicable pattern in whole blood; however, specific systemic responses may be shared between transcriptomic profiles. [Description provided by NIOSH]
• Subjects:
  Dust Ergonomics Hearing Loss, Noise-Induced Mining Occupational Health Safety Vehicle Emissions
• Keywords:
  Author Keywords: IPA Analysis Biomarkers Genes Hematopoiesis Laboratory Animals Lung Transcriptome Multi-walled Carbon Nanotubes MWCNT Pathology Pulmonary Effects Whole Blood Transcriptome

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• ISSN:
  0041-008X
• 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
• Volume:
  390
• NIOSHTIC Number:
  nn:20058492
• Citation:
  Toxicol Appl Pharmacol 2020 Mar; 390:114898
• Contact Point Address:
  Anna A. Shvedova, Health Effects Laboratory Division, NIOSH, CDC, Morgantown, WV
• Email:
  ats1@cdc.gov
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Mining
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:da48dede45cd1a853f6ea00999588422837cf8082bf7d87a34c852f6308eba07c257c594b8f1f1fba84df23820eea557aec0542e300ab50bd8d162ed87c62ae6
• Download URL:
  https://stacks.cdc.gov/view/cdc/221579/cdc_221579_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]