In vivo activation of a T helper 2-driven innate immune response in lung fibrosis induced by multi-walled carbon nanotubes

Details

• Personal Author:
  Dong J ; Ma Q
• Description:
  Pulmonary exposure to certain forms of carbon nanotubes (CNT) induces fibrosing lesions in the lungs that manifest an acute inflammation followed by chronic interstitial fibrosis. The mechanism of CNT-induced fibrogenesis is largely unknown. The biphasic development with drastically distinct pathologic manifestations suggests a junction of acute-to-chronic transition. Here we analyzed the molecular pathways and regulators underlying the pathologic development of CNT-induced lung fibrosis. Mice were exposed to multi-walled CNT (MWCNT; XNRI MWNT-7, Mitsui; 40 microg) by pharyngeal aspiration for 7 days along with vehicle and carbonaceous controls. Genome-wide microarray analyses of the lungs identified a range of differentially expressed genes that potentially function in the acute-to-chronic transition through pathways involving immune and inflammatory regulation, responses to stress and extracellular stimuli, and cell migration and adhesion. In particular, a T helper 2 (Th2)-driven innate immune response was significantly enriched. We then demonstrated that MWCNT induced the expression of Th2 cytokines interleukin (IL)-4 and IL-13, and a panel of signature downstream genes, such as Il4i1, Chia, and Ccl11/Eotaxin, time dependently. Induction of Th2 cytokines took place in CD4+ T lymphocytes indicating activation of Th2 cells. Furthermore, induction involved activation of a Th2 cell-specific signaling pathway through phosphorylation of STAT6 and up-regulation of GATA-3 to mediate the transcription of Th2 target genes. Our study uncovers activation of a Th2-driven immune/inflammatory response during pulmonary fibrosis development induced by MWCNT. The findings provide novel insights into the molecular events that control the transition from an acute inflammatory response to chronic fibrosis through Th2 functions in CNT-exposed lungs. [Description provided by NIOSH]
• Subjects:
  Construction Industry Environment Environmental Health Mining Occupational Health Safety
• Keywords:
  Author Keywords: Multi-walled Carbon Nanotubes Exposure Assessment Genes IL-4 IL-13 Immune Reaction In Vivo Study Laboratory Animals Lung Fibrosis Multi-walled Carbon Nanotubes MWCNT Nanotoxicology Pathology Pulmonary Fibrosis Th2-type Response

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• ISSN:
  0340-5761
• 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:
  90
• Issue:
  9
• NIOSHTIC Number:
  nn:20047956
• Citation:
  Arch Toxicol 2016 Sep; 90(9):2231-2248
• Contact Point Address:
  Qiang Ma, Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, CDC, Mailstop 3014, 1095 Willowdale Road, Morgantown, WV 26505, USA
• Email:
  qam1@cdc.gov
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Archives of Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8321f2534b68350141a78bd3697be2c967a6d89874a0d72e693d676dde553c659c64b0e96bc3738f8f6f506a641adfbfa0763a0d93897905f34e46d37e85a32a
• Download URL:
  https://stacks.cdc.gov/view/cdc/202875/cdc_202875_DS1.pdf
• File Type:
  [PDF - 3.39 MB ]