Molecular and Cellular Biochemistry

, Volume 200, Issue 1–2, pp 119–125

Dependence of NF-κB activation and free radical generation on silica-induced TNF-α production in macrophages

  • Yon Rojanasakul
  • Jiangping Ye
  • Fei Chen
  • Liying Wang
  • Ningli Cheng
  • Vincent Castranova
  • Val Vallyathan
  • Xiannglin Shi
Article

DOI: 10.1023/A:1007051402840

Cite this article as:
Rojanasakul, Y., Ye, J., Chen, F. et al. Mol Cell Biochem (1999) 200: 119. doi:10.1023/A:1007051402840

Abstract

Tumor necrosis factor α (TNFα) plays an important role in the pathogenesis of silicosis and other chronic inflammatory lung diseases. The present study investigates the role nuclear transcription factor κB (NF-κB) and oxygen free radicals in silica-induced TNFα production in primary alveolar macrophages and RAW 264.7 cells. Using electrophoretic mobility shift assay (EMSA) and enzyme-linked immunoadsorbent assay (ELISA), we have demonstrated that silica can induce NF-κB activation and TNFα expression in a dose-dependent manner. Transient transfection assays with a plasmid construct containing NF-κB binding sites linked to a reporter gene further show that silica is able to induce the transcriptional activation of NF-κB-dependent gene. Inhibition of NF-κB activation by SN50, a specific NF-κB blocker, abolishes silica-induced TNFα production. Pretreatment of the cells with catalase (H2O2 scavenger) or deferoxamine (·OH scavenger) effectively inhibits NF-κB and TNFα activation, whereas superoxide dismutase (O2- scavenger) has an opposite effect. These results indicate that silica-mediated free radical generation and NF-κB activation play important roles in silica-induced TNFα gene expression.

silica TNFα transcription factors NF-κB oxygen radicals 

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Yon Rojanasakul
    • 1
  • Jiangping Ye
    • 2
  • Fei Chen
    • 2
  • Liying Wang
    • 1
  • Ningli Cheng
    • 1
  • Vincent Castranova
    • 2
  • Val Vallyathan
    • 2
  • Xiannglin Shi
    • 2
  1. 1.Department of Basic Pharmaceutical SciencesWest Virginia University, Health Sciences CenterMorgantownUSA
  2. 2.Pathology and Physiology Research Branch, National Institute for Occupational Safety and HealthMorgantownUSA

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