Mesothelial Cell Autoantibodies Upregulate Transcription Factors Associated with Fibrosis

Details

• Alternative Title:
  Inhal Toxicol
• Personal Author:
  Gilmer, John ; Harding, Tanner ; Woods, Linda ; Black, Brad ; Flores, Raja ; Pfau, Jean
• Description:
  Amphibole asbestos exposure is associated with the production of mesothelial cell autoantibodies (MCAA). These MCAA have been linked with pleural fibrotic disease in the asbestos exposed community of Libby, Montana, and induce collagen deposition by cultured mesothelial cells. However, the exact intracellular mechanism by which these autoantibodies cause an increase in collagen deposition remains unknown. This study sought to gain insight into the transcription factors involved in the collagen production after human mesothelial cells are exposed to MCAA. In this study, transcription factor activation profiles were generated from human mesothelial cells (Met5A) treated with serum from Libby subjects, and were compared to cells treated with serum cleared of IgG, and therefore containing no MCAA. Analysis of those profiles indicated C/EBP-beta and hypoxia inducible factor 1 alpha (HIF-1α) are significantly increased in the nucleus, indicating activation, due to MCAA exposure compared to controls. Inhibition of either of these transcription factors significantly reduced collagen 1 deposition by these cells following exposure to MCAA. These data suggest autoantibodies are directly involved in type I collagen deposition and may elucidate potential therapeutic targets for autoantibody mediated fibrosis.
• Subjects:
  Amphibole Asbestos Asbestos, Amphibole Autoantibodies Autoimmunity CCAAT-Enhancer-Binding Protein-beta Cells, Cultured Collagen Epithelial Cells Fibrosis Gene Expression Humans Hypoxia-Inducible Factor 1, Alpha Subunit Occupational Exposure Pleural Fibrosis Serum Up-Regulation

  More +
• Source:
  Inhal Toxicol. 29(1):10-17.
• Pubmed ID:
  28183202
• Pubmed Central ID:
  PMC5554606
• Document Type:
  Journal Article
• Funding:
  P20 GM103408/GM/NIGMS NIH HHS/United States ; R01 TS000099/TS/ATSDR CDC HHS/United States ; R15 ES021884/ES/NIEHS NIH HHS/United States
• Volume:
  29
• Issue:
  1
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:c9131b97f7a5895752d3d81fe707d7c4d37b581874f26a0767802c8298289d8a
• Download URL:
  https://stacks.cdc.gov/view/cdc/47533/cdc_47533_DS1.pdf
• File Type:
  [PDF - 1.26 MB ]