Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Induction of TNFalpha in macrophages by vanadate is dependent on activation of transcription factor NF-KB and free radical reactions.

Authors
Ye-J; Ding-M; Zhang-X; Rojanasakul-Y; Nedospasov-S; Vallyathan-V; Castranova-V; Shi-X
Source
Mol Cell Biochem 1999 Aug; 198(2):193-200
NIOSHTIC No.
20027815
Abstract
Vanadium-induced TNFalpha production is believed to play an important role in respiratory disease associated with air pollution and occupational exposure. While vanadium is able to induce TNFalpha in macrophages or airway epithelial cells, the underlying mechanism is not well defined. In the present study, mechanisms of vanadate-induced TNFalpha production were analyzed in the murine Raw264.7 cells. Vanadate induces a significant amount of TNFalpha at both the protein and mRNA levels, and the induction is vanadate dose-dependent. The mechanism analysis was focused on transcriptional regulation of TNFalpha gene by vanadate. Transient transfection studies show that the TNFalpha gene promoter was activated by vanadate and this activation was associated with an increase in DNA binding activity of the nuclear factor-KB (NF-KB). Mutation of the NF-KB binding site in the gene promoter led to a loss of the promoter responsiveness to vanadate, indicating requirement of NF-KB. This is supported by evidence that inhibition of NF-KB activation by SN50, a specific NF-KB inhibitor, resulted in a decrease in the TNFalpha production. A role of reactive oxygen species (ROS) was explored in vanadate activity. The result shows that vanadate-induced TNFalpha production is elevated by NADPH, which enhances vanadate-mediated generation of ROS, but is inhibited by an antioxidant, N-acetyl-L-cysteine (NAC). Modification of TNFalpha production is associated with an enhancement or a repression of NF-KB activity by NADPH or NAC, respectively. Taken together, these results indicate that: (a) activation of the TNFalpha gene promoter contributes to the vanadate-induced TNFalpha production; (b) NF-KB is required for the vanadate-induced promoter activity of TNFalpha gene; (c) free radical reactions are involved in the vanadate-induced TNFalpha production and NF-KB activation.
Keywords
Respiratory-system-disorders; Respiratory-irritants; Pulmonary-disorders; Pulmonary-system-disorders; Nuclear-reactions; Environmental-exposure; Environmental-hazards; Environmental-pollution; Occupational-diseases; Occupational-exposure; Occupational-hazards; Occupational-health; Occupational-respiratory-disease; Vanadium-compounds; DNA-damage; Free-radicals; Lung-disorders; Lung; Laboratory-animals; Animal-studies; Animals; Statistical-analysis; Chemical-analysis; Analytical-chemistry; Analytical-methods; Analytical-models
CODEN
MCBIB8
CAS No.
7440-62-2
Publication Date
19990801
Document Type
Journal Article
Fiscal Year
1999
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0300-8177
NIOSH Division
HELD
Source Name
Molecular and Cellular Biochemistry
State
WV; MD
TOP