Iron inhibits the nitric oxide synthesis elicited by asbestos in murine macrophages

Our plain-English summary of Iron inhibits the nitric oxide synthesis elicited by asbestos in murine macrophages, by E. Aldieri, D. Ghigo, M. Tomatis, et al (Free Radical Biology & Medicine, 2001).

The study

• Authors: E. Aldieri, D. Ghigo, M. Tomatis, L. Prandi, I. Fenoglio, C. Costamagna, G. Pescarmona, A. Bosia, B. Fubini
• Journal: Free Radical Biology & Medicine
• Published: 2001;31(3):412-7
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Crocidolite fibers stimulated nitric oxide synthase (NOS) activity and expression in glial and alveolar murine macrophages: this effect was inhibited by iron supplementation and enhanced by iron chelation. We suggest that in these cells crocidolite stimulates NOS expression by decreasing the iron bioavailability and activating an iron-sensitive transcription factor.

In plain English

This laboratory study tested how iron affects production of nitric oxide, a reactive molecule made by immune cells, when mouse macrophages were exposed to crocidolite asbestos. The authors used two mouse macrophage cell lines grown in dishes: N11 glial cells and MH-S alveolar macrophages. Cells were incubated for 24 hours with UICC crocidolite fibers that were untreated, iron-enriched or iron-depleted, with or without iron-releasing compounds or the iron chelator desferrioxamine. In N11 cells, untreated crocidolite significantly increased nitric oxide synthase activity and nitrite production compared with controls. These effects were significantly reduced with iron-enriched fibers or an added iron donor. Iron-depleted fibers were more effective than untreated fibers. Desferrioxamine alone also raised nitric oxide production, and added iron reversed this. MH-S cells showed a similar pattern. Crocidolite raised levels of the inducible enzyme protein, but iron-enriched fibers did not significantly do so. The authors suggested that their data point to crocidolite stimulating nitric oxide synthesis by decreasing iron availability in these cells, possibly through an iron-sensitive transcription factor. That factor was not identified or tested in this study.

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: Two mouse (murine) macrophage cell lines grown in culture: N11 glial cells and MH-S alveolar macrophages, at the University of Torino, Italy
• Exposure: UICC crocidolite fibers for 24 hours. The fibers were native, iron-enriched (a 15% increase in iron content) or iron-depleted (about 6% of total iron mobilized). Some cultures also received the iron-releasing compounds ferric nitrilotriacetate (Fe-NTA) and ferric citrate, or the iron chelator desferrioxamine (DFX). Lipopolysaccharide (LPS) was used for comparison.
• Main results:
  • In N11 cells, native crocidolite significantly increased nitric oxide synthase (NOS) activity and nitrite production compared with controls.
  • In N11 cells, these effects were significantly decreased with iron-enriched crocidolite, or with native crocidolite plus an iron donor (Fe-NTA or ferric citrate).
  • In N11 cells, crocidolite combined with DFX showed no synergistic effect, but iron-depleted crocidolite was more effective than native crocidolite.
  • MH-S cells showed a similar response pattern. In these cells DFX significantly increased extracellular nitrite (15.92 plus or minus 0.4, p less than .01 versus control, n = 6). Adding Fe-NTA reversed this (6.04 plus or minus 0.3, not significant versus control, n = 6).
  • In both cell types, LPS or native crocidolite significantly increased iNOS protein. Iron-enriched crocidolite did not significantly increase it. Iron-depleted crocidolite gave iNOS protein expression superimposable on that of native crocidolite. In N11 cells, iNOS mRNA (by RT-PCR) followed the same pattern.
  • Iron also reduced LPS-induced nitrite. In N11 cells, nitrite (nmol per 24 h per mg cell protein) was 8.62 in controls, 86.45 with LPS, and 40.1 with LPS plus Fe-NTA (p less than .01 versus LPS).
• The authors' conclusion: The authors suggested that their data indicate that, in N11 and MH-S macrophages, crocidolite stimulates nitric oxide synthesis by decreasing iron availability. They proposed, without testing it, that this may occur through activation of an iron-sensitive transcription factor such as NF-IL6 or HIF-1. They also suggested that asbestos, depending on tissue type and intracellular conditions, can act as a two-way exchanger of iron with its surroundings.
• Limitations the authors state:
  • The authors stated that the specific transcription factor involved had not yet been identified and that experiments to identify it were under way.

Topics

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

Medical terms in this study, explained in our Lexicon: Macrophage, Crocidolite.

Related studies

• Nitric oxide (NO) synthase activity in the lung and NO synthesis in alveolar macrophages of rats increased on exposure to asbestos — H. Iguchi, S. Kojo, et al. (1996)
• Asbestos fibers and interferon-gamma up-regulate nitric oxide production in rat alveolar macrophages — G. Thomas, T. Ando, et al. (1994)
• Dual role of inducible nitric oxide synthase in acute asbestos-induced lung injury — M. Dörger, A.M. Allmeling, et al. (2002)
• Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells — E. Aldieri, S. Orecchia, et al. (2004)
• Mechanisms of asbestos-induced nitric oxide production by rat alveolar macrophages in inhalation and in vitro models — T.R. Quinlan, K.A. BeruBe, et al. (1998)
• Regulation of nitric oxide synthase induction by iron and glutathione in asbestos-treated human lung epithelial cells — S.H. Park, A.E. Aust (1998)

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