Molecular Mechanism of Tumor Necrosis Factor-α Production in 1→3-β-Glucan (Zymosan)-activated Macrophages

Shih Houng Young, Jianping Ye, David G. Frazer, Xianglin Shi, Vince Castranova

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

Abstract

The molecular details of 1→3-β-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)-α production after glucan stimulation of macrophages. We demonstrated that activation of nuclear factor κB (NF-κB) is essential in zymosan A (a source of 1→-β-glucans)-induced TNF-α production in macrophages (RAW264.7 cells). Zymosan A-induced TNF-α protein production was associated with an increase in the TNF-α gene promoter activity. Activation of the TNF-α gene promoter was dependent on activation of NF-κB. Time course studies indicated that DNA binding activity of NF-κB preceded TNF-α promoter activity. Inhibition of NF-κB activation led to a dramatic reduction in both TNF-α promoter activity and TNF-α protein production in the response to zymosan A. Mutation of a major NF-κB binding site (κ3) 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-κB is involved in signal transduction of 1→3-β-glucans-induced TNF-α expression.

Original languageEnglish
Pages (from-to)20781-20787
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number23
DOIs
StatePublished - Jun 8 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Molecular Mechanism of Tumor Necrosis Factor-α Production in 1→3-β-Glucan (Zymosan)-activated Macrophages'. Together they form a unique fingerprint.

Cite this