Th2-driven innate immune responses in the development of lung fibrosis induced by multi-walled carbon nanotubes

Details

• Personal Author:
  Dong J ; Ma Q
• Description:
  Aberrant tissue responses to persistent deposition of foreign bodies lead to organ fibrosis through orchestrated, yet poorly understood, mechanisms. We used multi-walled carbon nanotubes (MWCNT) to develop a mouse model of lung fibrosis, which features a prominent acute phase inflammation followed by chronic interstitial fibrosis. Genome-wide microarray analyses of the lungs exposed to MWCNT identified a range of differentially expressed genes that potentially function in the regulation of the acute-to-chronic transition, through pathways of immune and inflammatory regulation, response to stress and extracellular stimuli, and cell migration and adhesion. In particular, T helper 2 (Th2)-driven innate immune responses were 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 including 114i1, Chia, and Ccll 1/ Eotaxin. Induction ofTh2 cytokines took place in CD4+ T lymphocytes indicating the activation ofTh2 cells. Furthermore, induction involved the activation of STAT6 via phosphorylation of STAT6 and up-regulation of GATA- 3 that controls the transcription ofTh2 target genes. Our study uncovers the activation ofTh2-driven immune/inflammatory responses during pulmonary pathologic fibrosis development induced by MWCNT. [Description provided by NIOSH]
• Subjects:
  Animals Blood Fibrosis Genetics Laboratories Lung Lung Diseases Occupational Health Pathology Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Cytokines Genes Laboratory Animals Lung Fibrosis Lung Tissue Lymphocytes Multi-walled Carbon Nanotubes MWCNT Pulmonary Disorders Pulmonary System Pulmonary System Disorders Stress Tissue Culture

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• Publisher:
  Keystone Symposia
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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:
  81
• NIOSHTIC Number:
  nn:20048453
• Citation:
  Fibrosis: from basic mechanisms to targeted therapies joint with the meeting on stromal cells in immunity, Feb 7-11, 2016, Keystone, Colorado. Silverthorne, CO: Keystone Symposia, 2016 Feb; :81
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  Fibrosis: from basic mechanisms to targeted therapies joint with the meeting on stromal cells in immunity, Feb 7-11, 2016, Keystone, Colorado
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c32793df7e085aff6fe5fd928bce8dfff80aa9f4b4a626fa19e814a72aaba3fec6e2c2273d9773e1ec25db8bfca1c454bda5f774ad66d1bb856e4bba15b1df32
• Download URL:
  https://stacks.cdc.gov/view/cdc/203204/cdc_203204_DS1.pdf
• File Type:
  [PDF - 595.66 KB ]