Induction of manganese superoxide dismutase gene expression in bronchoepithelial cells after rockwool exposure

Our plain-English summary of Induction of manganese superoxide dismutase gene expression in bronchoepithelial cells after rockwool exposure, by J. Marks-Konczalik, A. Gillissen, M. Jaworska, et al (Lung, 1998).

The study

• Authors: J. Marks-Konczalik, A. Gillissen, M. Jaworska, S. Löseke, B. Voss, A. Fisseler-Eckhoff, I. Schmitz, G. Schultze-Werninghaus
• Journal: Lung
• Published: 1998;176(3):165-80
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Superoxide dismutases play an important protective role in the lung defense against the pro-oxidative effect of fibrous dusts (e.g. crocidolite fibers). Particularly crocidolite, but also other asbestos fibers, are known to induce cellular antioxidant defense. Although rockwool, a man-made fiber made from rock, is used widely for insulation purposes, its effects on the superoxide dismutases in bronchoepithelial cells have not been investigated. Thus, the purpose of this study was to determine whether human bronchoepithelial cells (BEAS 2B) respond to rockwool fibers (115-4 experimental rockwool fiber) by induction of MnSOD mRNA and an increase of MnSOD activity levels. The results were compared with BEAS 2B cells exposed to silica (alpha-quartz: DQ12; SiO2) and UICC (Union Internationale Contre le Cancer) crocidolite (concentrations of all dusts: 0, 2, 5, 10, 25, 50 micrograms/cm2 = 0, 2.4, 6, 12, 30, 60 micrograms/ml; 24-h exposure) as control fibers. Scanning electron microscopy confirmed close dust cell contact under all experimental settings. Very low MnSOD mRNA baseline levels rose significantly (p < 0.001) in BEAS 2B cells exposed to all three dusts at 2 micrograms/cm2. However, at > 25 micrograms/cm2 MnSOD mRNA levels in silica- and crocidolite- but not in rockwool-exposed cells decreased. Slight (no significance) increases of MnSOD activity were observed which decreased at higher dust (> 5 micrograms/cm2) concentrations. These results suggest that: (1) like crocidolite and silica, rockwool accelerates MnSOD gene expression in bronchoepithelial cells; (2) an increase of MnSOD mRNA levels is not accompanied by MnSOD activity elevation; (3) in contrast to rockwool, high concentrations (> or = 25 micrograms/cm2) of crocidolite and silica reduced MnSOD activity and MnSOD mRNA levels. Because oxidants (H2O2) and crocidolite fibers were shown to reduce SOD activity, lack of active MnSOD protein may be caused by inactivation on a post-translational level. Furthermore, the decline of MnSOD mRNA and MnSOD activity levels coincides with increasing cytotoxicity. In conclusion, rockwool was demonstrated to induce MnSOD gene expression, perhaps because of its pro-oxidative effect in bronchoepithelial cells. In contrast to crocidolite and silica, rockwool fibers are not cytotoxic in this experimental setting.

In plain English

This was a laboratory experiment on cells, not a study of people. The authors exposed BEAS 2B cells, a line derived from normal human airway lining, for 24 hours to an experimental rockwool fiber (115-4). They used UICC crocidolite asbestos and silica (quartz) as comparison dusts, at doses from 0 to 50 micrograms per square centimetre. They measured messenger RNA for the antioxidant enzyme manganese superoxide dismutase (MnSOD), its activity, and cell damage. All three dusts significantly raised MnSOD messenger RNA. With rockwool it stayed raised at every dose. It fell at higher doses of crocidolite (above 5) and silica (above 25). Enzyme activity rose only slightly, and not significantly: from a baseline of 34.4 to at most 46.5 milliunits per mg protein with rockwool. Rockwool was nontoxic to the cells up to 100 micrograms per square centimetre. At that dose, a cytotoxicity index based on release of the enzyme LDH rose to 37.4 ± 6.6% with crocidolite and 11.2 ± 1.5% with silica. The authors concluded that rockwool induced MnSOD gene expression. They took this as indirect evidence that rockwool has biologic effects mediated by oxidants.

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: BEAS 2B cells, an SV40-immortalized human bronchial epithelial cell line; Northern blot experiments were run in four trials
• Exposure: 115-4 experimental rockwool fiber, with UICC crocidolite and DQ12 silica (alpha-quartz) as positive controls. All three were given at 0, 2, 5, 10, 25 and 50 micrograms per square centimetre for 24 hours.
• Main results:
  • In unexposed cells, MnSOD messenger RNA was very low. After 24-hour exposure to crocidolite, silica or rockwool, it rose significantly (p less than 0.001).
  • With rockwool, MnSOD messenger RNA was increased at every tested concentration. At 50 it remained elevated.
  • MnSOD messenger RNA peaked at 5 for crocidolite and at 25 for silica. It then decreased at higher concentrations of crocidolite (above 5) and silica (above 25).
  • Baseline MnSOD activity was 34.4 ± 11.2 milliunits/mg total protein. Maximum levels were 39.5 ± 7.3 with crocidolite at 2, 43.3 ± 6.4 with silica at 10, and 46.5 ± 7.0 with rockwool at 2. These increases over baseline were not statistically significant.
  • At the highest concentrations, MnSOD activity declined. The decline was significantly smaller after rockwool than after crocidolite or silica (p less than 0.05).
  • In cell-free tests, crocidolite combined with hydrogen peroxide lowered SOD enzyme activity by about 70%. Crocidolite alone did not reduce it, and neither did the lower hydrogen peroxide concentration alone.
  • Rockwool was nontoxic to the cells at all concentrations tested (2 to 100). At 100, the LDH-release cytotoxicity index rose significantly from less than 2%: to 37.4 ± 6.6% with crocidolite and to 11.2 ± 1.5% with silica. With crocidolite at 50, the index was 17.5 ± 8.3%.
  • Scanning electron microscopy showed close contact between the cells and all three dusts.
• The authors' conclusion: The authors concluded that their results give indirect evidence supporting the hypothesis that rockwool has biologic effects mediated by oxidants. They also concluded that, unlike crocidolite and silica, rockwool was virtually nontoxic to the cells.
• Limitations the authors state:
  • The authors noted that MnSOD induction depends strongly on cell type and exposure conditions. Their results may therefore reflect a phenomenon unique to bronchoepithelial 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: Superoxide, Crocidolite, UICC, Scanning Electron Microscopy (SEM).

Related studies

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• Manganese superoxide dismutase in human pleural mesothelioma cell lines — V.L. Kinnula, P. Pietarinen-Runtti, et al. (1996)
• Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma — K. Kahlos, S. Anttila, et al. (1998)
• Analysis of asbestos-induced gene expression changes in bronchiolar epithelial cells using laser capture microdissection and quantitative reverse transcriptase-polymerase chain reaction — C.B. Manning, B.T. Mossman, et al. (2006)
• Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma — S. Landi, F. Gemignani, et al. (2007)
• Asbestos exposure, manganese superoxide dismutase (MnSOD) genotype, and lung cancer risk — L.I. Wang, D. Neuberg, et al. (2004)

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