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

Our plain-English summary of Crocidolite activates NF-kappa B and MIP-2 gene expression in rat alveolar epithelial cells. Role of mitochondrial-derived oxidants, by K.E. Driscoll, J.M. Carter, B.W. Howard, et al (Environmental Health Perspectives, 1998).

The study

• Authors: K.E. Driscoll, J.M. Carter, B.W. Howard, D. Hassenbein, Y.M. Janssen, B.T. Mossman
• Journal: Environmental Health Perspectives
• Published: 1998;106 Suppl 5(Suppl 5):1171-4
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a laboratory study of rat lung cells grown in culture dishes, not a study of people or live animals. The authors exposed a rat alveolar type II cell line, called RLE-6TN, to crocidolite asbestos at 10 micrograms per square centimeter for 6 hours. They measured NF-kappa B, a protein that switches on inflammation-related genes, by its binding activity in the cell nucleus. They also measured the level of messenger RNA from the gene for MIP-2, a signal that attracts white blood cells called neutrophils. Crocidolite increased both. The antioxidant tetramethylthiourea (TMTU) at 50 millimolar reduced both responses. At 25 millimolar it did not markedly reduce the NF-kappa B response. Crocidolite raised the cells' release of hydrogen peroxide approximately 1.8-fold. That rise was reduced by TTFA, a chemical that blocks part of the energy-producing chain in mitochondria. TTFA at 200 micromolar, and to a lesser extent at 20 micromolar, also reduced NF-kappa B activation, and TTFA reduced the MIP-2 response. The authors concluded that oxidants from mitochondria play a role in the signaling by which crocidolite triggers these responses in rat alveolar cells.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell culture experiment
• Who was studied: Cultured cells of the rat alveolar type II cell line RLE-6TN (no humans or live animals)
• Exposure: Crocidolite asbestos at 10 micrograms per square centimeter of culture dish for 6 hours, with or without the antioxidant TMTU (25 or 50 millimolar) or the mitochondrial respiratory chain inhibitor TTFA (20 or 200 micromolar)
• Main results:
  • In RLE-6TN cells, crocidolite increased nuclear NF-kappa B binding activity. TMTU at 50 mM, but not at 25 mM, markedly reduced this response.
  • TTFA at 200 micromolar, and to a lesser extent at 20 micromolar, reduced crocidolite-induced NF-kappa B activation in RLE-6TN cells.
  • Crocidolite increased hydrogen peroxide release by RLE-6TN cells approximately 1.8-fold.
  • TTFA inhibited the crocidolite-induced increase in hydrogen peroxide production by RLE-6TN cells.
  • Crocidolite increased MIP-2 mRNA (but not the control gene GAPDH) in RLE-6TN cells.
  • TMTU at 50 mM and TTFA at 200 micromolar reduced the crocidolite-induced increase in MIP-2 mRNA.
• The authors' conclusion: The authors concluded that oxidants derived from mitochondria play a role in the signaling pathway by which crocidolite increases NF-kappa B activation and MIP-2 gene expression in rat alveolar type II cells.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Crocidolite, Nuclear Factor kappa B (NF-κB), Cytokine, Translocation, Oxidative Stress.

Related studies

• Modulation of mitochondrial gene expression in pulmonary epithelial cells exposed to oxidants — Y.M. Janssen, K.E. Driscoll, et al. (1998)
• Asbestos induces nuclear factor kappa B (NF-kappa B) DNA-binding activity and NF-kappa B-dependent gene expression in tracheal epithelial cells — Y.M. Janssen, A. Barchowsky, et al. (1995)
• Mitochondria-targeted Ogg1 and aconitase-2 prevent oxidant-induced mitochondrial DNA damage in alveolar epithelial cells — S.J. Kim, P. Cheresh, et al. (2014)
• Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos — H.N. Kim, Y. Morimoto, et al. (2001)
• Possible role of lipid peroxidation in the induction of NF-kappa B and AP-1 in RFL-6 cells by crocidolite asbestos: evidence following protection by vitamin E — S.P. Faux, P.J. Howden (1997)
• Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage — S.J. Kim, P. Cheresh, et al. (2016)

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