Molecular Mechanism of Tumor Necrosis Factor-Alpha Production in 1–>3-B-Glucan (Zymosan)-Activated Macrophages

Details

• Personal Author:
  Castranova, Vincent ; Frazer DG ; Shi X ; Ye J ; Young SH
• Description:
  The molecular details of 1-->3-beta-glucans, a fungal cell wall component, induced inflammatory responses are not well understood. In the present study, we conducted a systematic analysis of the molecular events leading to tumor necrosis factor (TNF)-alpha production after glucan stimulation of macrophages. We demonstrated that activation of nuclear factor kappaB (NF-kappaB) is essential in zymosan A (a source of 1-->3-beta-glucans)-induced TNF-alpha production in macrophages (RAW264.7 cells). Zymosan A-induced TNF-alpha protein production was associated with an increase in the TNF-alpha gene promoter activity. Activation of the TNF-alpha gene promoter was dependent on activation of NF-kappaB. Time course studies indicated that DNA binding activity of NF-kappaB preceded TNF-alpha promoter activity. Inhibition of NF-kappaB activation led to a dramatic reduction in both TNF-alpha promoter activity and TNF-alpha protein production in the response to zymosan A. Mutation of a major NF-kappaB binding site (kappa3) in the gene promoter resulted in a significant decrease in the induction of the gene promoter by zymosan A, while mutation of Egr or CRE sites failed to inhibit the response to zymosan. Together, these results strongly suggest that NF-kappaB is involved in signal transduction of 1-->3-beta-glucans-induced TNF-alpha expression. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Genetics Occupational Health Safety
• Keywords:
  Cell-biology Cell-cultures Cell-function Cellular-function Cellular-reactions Gene-mutation Genes
• ISSN:
  0021-9258
• 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:
  276
• Issue:
  23
• NIOSHTIC Number:
  nn:20021937
• Citation:
  J Biol Chem 2001 Jun; 276(23):20781-20787
• Email:
  syoung@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-512:2c69a6f1045d74bb29e0f7d9d10a193fa053d2a239b2d2c8c83a56c27de51e906681e68d923104de2bf69e90a2e4623bfceb8a7244dabd120f2e2b060ba15ea2
• Download URL:
  https://stacks.cdc.gov/view/cdc/199011/cdc_199011_DS1.pdf
• File Type:
  [PDF - 445.98 KB ]