Induction of TNFalpha in Macrophages by Vanadate Is Dependent on Activation of Transcription Factor NF-KB and Free Radical Reactions

Details

• Personal Author:
  Castranova, Vincent ; Ding M ; Nedospasov S ; Rojanasakul Y ; Shi X ; Vallyathan V ; Ye J ; Zhang X
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Chemistry Chemistry, Analytic DNA Environmental Exposure Environmental Pollution Free Radicals Irritants Laboratories Lung Lung Diseases Occupational Diseases Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety Vanadium Compounds

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• Keywords:
  Analytical-chemistry Analytical-methods Analytical-models Animal-studies Chemical-analysis DNA-damage Environmental-exposure Environmental-hazards Environmental-pollution Free-radicals Laboratory-animals Lung-disorders Nuclear-reactions Occupational-diseases Occupational-exposure Occupational-hazards Occupational-health Occupational-respiratory-disease Pulmonary-disorders Pulmonary-system-disorders Respiratory-irritants Respiratory-system-disorders Statistical-analysis Vanadium-compounds

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• ISSN:
  0300-8177
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; 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
• Pages in Document:
  193-200
• Volume:
  198
• Issue:
  2
• NIOSHTIC Number:
  nn:20027815
• Citation:
  Mol Cell Biochem 1999 Aug; 198(2):193-200
• CAS Registry Number:
  Vanadium (CAS RN 7440-62-2)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  True
• Source Full Name:
  Molecular and Cellular Biochemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:47d6b5fe19f862396cfcb0fe76b31886d856d4860af8e436a9988c2feae8debf97be9ba4ee7efd916560391953d215ec1fff06b1c1d8bae609ac297ce882a0c4
• Download URL:
  https://stacks.cdc.gov/view/cdc/197670/cdc_197670_DS1.pdf
• File Type:
  [PDF - 70.67 KB ]