Crocidolite activates NF-kappa B and MIP-2 gene expression in rat alveolar epithelial cells. Role of mitochondrial-derived oxidants

Environ Health Perspect. 1998 Oct;106 Suppl 5(Suppl 5):1171-4. doi: 10.1289/ehp.98106s51171.

Abstract

Nuclear factor kappa B (NF-kappa B) is a transcription factor that regulates expression of several genes coding for inflammatory and immunoregulatory proteins including the neutrophil chemotactic cytokine MIP-2. In previous studies we found that crocidolite asbestos activates the nuclear translocation of NF-kappa B as well as MIP-2 gene expression in rat alveolar type II cells. Here we report that both crocidolite-induced NF-kappa B activation of MIP-2 gene expression can be attenuated by the antioxidant tetramethylthiourea, suggesting the dependence of these responses on oxidative stress. Crocidolite exposure of RLE-TN cells also increased production of H2O2, a response that was inhibited by the mitochondrial respiratory chain inhibitor thenoyltrifluoroacetone (TTFA). TTFA treatment of RLE-6TN cells also inhibited crocidolite-induced nuclear translocation of NF-kappa B and MIP-2 gene expression. These results indicate crocidolite exposure of rat alveolar type II cells results in increased production of mitochondrial-derived hydrogen peroxide and that mitochondrial-derived oxidants contribute to crocidolite activation of NF-kappa B and increases in MIP-2 gene expression.

MeSH terms

  • Animals
  • Asbestos, Crocidolite / toxicity*
  • Base Sequence
  • Cell Line
  • Chemokine CXCL2
  • Chemokines / genetics*
  • DNA Primers / genetics
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / drug effects
  • Hydrogen Peroxide / metabolism
  • Mitochondria / metabolism
  • NF-kappa B / genetics*
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / drug effects*
  • Pulmonary Alveoli / metabolism*
  • Rats
  • Superoxides / metabolism

Substances

  • Chemokine CXCL2
  • Chemokines
  • Cxcl2 protein, mouse
  • DNA Primers
  • NF-kappa B
  • Superoxides
  • Asbestos, Crocidolite
  • Hydrogen Peroxide