Induction of nuclear translocation of NF-kappaB in epithelial cells by respirable mineral fibres

J Pathol. 1999 Oct;189(2):258-64. doi: 10.1002/(SICI)1096-9896(199910)189:2<258::AID-PATH410>3.0.CO;2-E.


A panel of mineral fibres has been studied for their ability to cause translocation of the transcription factor NF-kappaB to the nucleus in A549 lung epithelial cells. On the basis of inhalation studies, three fibres were designated as being carcinogenic-amosite asbestos, silicon carbide and refractory ceramic fibre 1 (RCF1)-or non-carcinogenic-man-made vitreous fibre (MMVF10), Code 100/475 glass fibre, and RCF4. The experiments were carried out at equal fibre number. It was hypothesized that carcinogenic fibres have greater free radical activity than non-carcinogenic fibres and that an oxidative stress produced in the lung after inhalation of fibres could cause translocation of the transcription factor NF-kappaB to the nucleus, where transcription of pro-inflammatory genes such as cytokines could occur. It was demonstrated that a simple oxidant, hydrogen peroxide, caused translocation in a time- and dose-dependent manner. The three carcinogenic fibres produced a significant dose-dependent translocation of NF-kappaB to the nucleus, whereas the non-carcinogenic fibres did not. Silicon carbide fibres were the most potent of the pathogenic fibres. MMVF10 was the most potent of the non-pathogenic fibres, causing significant nuclear translocation of NF-kappaB at high fibre number. Using three antioxidants, curcumin, pyrrolidine dithiocarbamate, and Nacystelin, translocation caused by carcinogenic fibres could be significantly reduced. The present study shows that a short-term in vitro assay can discriminate between pathogenic and non-pathogenic fibres in terms of a key pro-inflammatory event in epithelial cells. The mechanism of the activation of NF-kappaB by pathogenic fibres and its general applicability to other fibre types remain to be determined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology
  • Carcinogens / antagonists & inhibitors
  • Carcinogens / toxicity*
  • Cell Culture Techniques
  • Dose-Response Relationship, Drug
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Mineral Fibers / toxicity*
  • NF-kappa B / metabolism*


  • Antioxidants
  • Carcinogens
  • Mineral Fibers
  • NF-kappa B
  • Hydrogen Peroxide