Role of transcription factor NF-κB in asbestos-induced TNFα response from macrophages

Ningli Cheng, Xianglin Shi, Jianping Ye, Vincent Castranova, Fei Chen, Stephen S. Leonard, Val Vallyathan, Yon Rojanasakul

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Asbestos exposure in humans is associated with inflammatory, fibrotic, and malignant diseases in the lung. Increasing evidence supports the hypothesis that the production of proinflammatory cytokines such as tumor necrosis factor-α (TNFα) is an important mediator of the pathologic responses of asbestosis. In this study, we examine the role of nuclear transcription factor-κB (NF-κB) and free oxygen radicals in asbestos- induced TNFα gene and protein expression in lung macrophages. Exposure of the cells to crocidolite asbestos caused a parallel increase in TNFα production and NF-κB activation, as analyzed by enzyme-linked immunosorbent assay and electrophoretic mobility shift assay. Inhibition of NF-κB by SN50, an inhibitor of NF-κB nuclear translocation, or by sequence-specific oligonucleotides directed against the NF-κB binding site of TNFα promoter attenuated the asbestos effect on TNFα production. Gene transfection assays using an expression plasmid containing a luciferase reporter gene and a TNFα-derived NF-κB gene promoter further indicated the dependence of NF-κB activation on asbestos-reduced gene expression. The effects of asbestos on NF-κB and TNFα activation were inhibited by oxygen radical scavengers and were enhanced by antioxidant enzyme inhibitors. These results indicate that asbestos-induced TNFα gene expression is mediated through a process that involves NF-κB activation and free radical reactions.

Original languageEnglish
Pages (from-to)201-210
Number of pages10
JournalExperimental and Molecular Pathology
Issue number3
StatePublished - Aug 1999

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grant HL54291 and by the National Institute of Occupational Safety and Health.

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry


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