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Molecular mechanism of tumor necrosis factor-alpha production in 1-->3-B-glucan (zymosan)-activated macrophages.

Authors
Young-SH; Ye-J; Frazer-DG; Shi-X; Castranova-V
Source
J Biol Chem 2001 Jun; 276(23):20781-20787
NIOSHTIC No.
20021937
Abstract
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.
Keywords
Genes; Gene-mutation; Cell-cultures; Cell-biology; Cell-function; Cellular-function; Cellular-reactions
CODEN
JBCHA3
Publication Date
20010608
Document Type
Journal Article
Email Address
syoung@cdc.gov
Fiscal Year
2001
NTIS Accession No.
NTIS Price
Issue of Publication
23
ISSN
0021-9258
NIOSH Division
HELD
Source Name
Journal of Biological Chemistry
State
WV
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