Activation of Mitogen-Activated Protein Kinase p38 and Extracellular Signal-Regulated Kinase Is Involved in Glass Fiber-Induced Tumor Necrosis Factor-Alpha Production in Macrophages

Details

• Personal Author:
  Baron, Paul A. ; Castranova, Vincent ; Jones, William G. ; Martinez AB ; Robinson VA ; Shi X ; Ye J ; Young S ; Zeidler PC
• Description:
  In a previous study, we demonstrated that the length of glass fibers was a critical determinant of fiber potency in induction of tumor necrosis factor (TNF)-alpha and that activation of NF-kappaB was an important factor in this response. In the present study, we analyzed the role of mitogen-activated protein (MAP) kinases in the induction of TNF-alpha by glass fibers. Glass fibers induced phosphorylation of MAP kinases, p38, and ERK in primary rat alveolar macrophages, and this phosphorylation was associated with TNF-alpha gene expression. Long fibers were more potent than short fibers in activation of MAP kinases. Results from mechanistic analysis support that MAP kinases activate transcription factor c-Jun. The activated c-Jun acts on the TNF-alpha gene promoter through two binding sites, the cyclic AMP response element and the activator protein 1-binding site. These results suggest that in addition to the NF-kappaB pathway for TNF-alpha production, glass fibers are able to activate c-Jun through MAP kinase pathways that lead to induction of TNF-alpha expression. [Description provided by NIOSH]
• Subjects:
  Carcinogens Cell Division Genetics Glass Occupational Health Safety
• Keywords:
  Carcinogenesis Carcinogenicity Cell-biology Cell-division Cell-function Cellular-function Fiberglass-industry Genes Glass-products
• ISSN:
  0021-9258
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; DRDS - Division of Respiratory Disease Studies ; DART - Division of Applied Research and Technology
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  276
• Issue:
  7
• NIOSHTIC Number:
  nn:20021934
• Citation:
  J Biol Chem 2001 Feb; 276(7):5360-5367
• Email:
  vic1@cdc.gov
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Biological Chemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e88198a1f176ec164dc40e0e4d8e876aa8bd1c7f5d1f0ea4de90e1f90de3d2af4d05dc5956119716cb9ab19e3a235026861f9cf22095a46137397fee75a8485d
• Download URL:
  https://stacks.cdc.gov/view/cdc/199008/cdc_199008_DS1.pdf
• File Type:
  [PDF - 244.08 KB ]