The Role of NF-kappaB in 1–>3-Beta-Glucan(zymosan)induced TNF-Alpha Production

Details

• Personal Author:
  Castranova, Vincent ; Frazer DG ; Shi X ; Ye J ; Young S
• Description:
  The signal transduction pathway of inflammatory response to 1-->3-beta-glucans, a fungal cell wall component, is not well understood. Tumor necrosis factor (TNF)-alpha is an important cytokine in inflammation. The present study used zymosan A (a source of 1-->3-beta-glucans)-induced TNF-alpha production as a model to explore the signal transduction pathway of 1-->3-beta-glucans. The results show that zymosan A induced TNF-alpha production by mouse macrophage RAW264.7 cells in a time- and concentration- dependent pattern. The optimal concentration of zymosan A was 100 micrograms/ml for TNF-alpha simulation. The TNF-alpha level reached a plateau around 12.5 hrs. in the cell culture medium. The mechanism of zymosan A-induced TNF-alpha production was investigated at the gene transcription level. The gel shift assay was used to examine the DNA-binding activity of NF-kappaB in the zymosan A-treated cells. The results showed that NF-kappaB activity was increased by zymosan A, and this activity was associated with TNF-alpha production. Aluciferase reporter controlled by the TNF-alpha promoter was utilized to examine promoter activity of the TNF-alpha gene in transiently transfected RAW264.7 cells. The results demonstrated that zymosan A could activate the gene promoter and the induced-promoter activity peaked and 24 hours after zymosan A stimulation. The promoter response depended on the NF-kappaB binding site as verified by using a NFkappaB inhibitor (caffeic acid phenethyl ester) and by mutation of the NF-kappaB binding site in the promoter. Combined together, these results suggest that activation of NF-kappaB is a very important pathway by which zymosan A induces TNF-alpha expression. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Fungi Genetics Occupational Health Safety
• Keywords:
  Cell-cultures Fungal-diseases Fungal-infections Genes
• ISSN:
  1059-2644
• Publisher:
  National Cotton Council
• Document Type:
  Text
• Genre:
  Proceedings
• Place as Subject:
  Ohio ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 6 ; Tennessee ; Texas
• 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:
  241-247
• Volume:
  1
• NIOSHTIC Number:
  nn:20000913
• Citation:
  Cotton and Other Organic Dusts: Proceedings of the Twenty-fourth Cotton and Organic Dusts Research Conference, Beltwide Cotton Conferences, January 4 - 8, 2000, San Antonio, Texas. Memphis, TN: National Cotton Council, 2000 Jan; 1:241-247
• Editor(s):
  Wakelyn PJ; Jacobs RR; Rylander R
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  False
• Source Full Name:
  Cotton and Other Organic Dusts: Proceedings of the Twenty-fourth Cotton and Organic Dusts Research Conference, Beltwide Cotton Conferences, January 4 - 8, 2000, San Antonio, Texas
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a747553cf7e47c8b062e02a2d70fc06ab322b02d98e60dc73f3810e077bdb09c5fe3e59b8c2b29709ad3119b07f80aeddf4655de48c43528ae47630dbf4f4304
• Download URL:
  https://stacks.cdc.gov/view/cdc/198256/cdc_198256_DS1.pdf
• File Type:
  [PDF - 165.17 KB ]