Multinucleation and pro-inflammatory cytokine release promoted by fibrous fluoro-edenite in lung epithelial A549 cells

Our plain-English summary of Multinucleation and pro-inflammatory cytokine release promoted by fibrous fluoro-edenite in lung epithelial A549 cells, by S. Travaglione, B.M. Bruni, L. Falzano, et al (Toxicology in Vitro, 2006).

The study

• Authors: S. Travaglione, B.M. Bruni, L. Falzano, P. Filippini, A. Fabbri, L. Paoletti, C. Fiorentini
• Journal: Toxicology in Vitro
• Published: 2006;20(6):841-50
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

An unusual cluster of malignant mesothelioma was evidenced in Biancavilla, a Sicily village where no inhabitant had been significantly and professionally exposed to asbestos. Mineralogical and environmental studies led to the identification of a new prismatic amphibole, named fluoro-edenite. We previously reported, by using the human lung epithelial A549 cells, that prismatic fluoro-edenite was unable to induce changes that could be somehow related to cellular transformation, and this was in accordance with studies carried out in vivo. More recently, a fibrous amphibole with a composition very similar to that of prismatic fluoro-edenite, was identified in Biancavilla. This fibrous fluoro-edenite was shown to induce mesothelioma in rats. In keeping with this effect in vivo, in the present work we observed multinucleation and spreading, common features of transformed cells, as well as pro-inflammatory cytokine release in A549 cells. Such cell changes occurred without interfering with the passage of the resulting multinucleated cells through the cell cycle and without condemning cells to death. Hence, in lung epithelial cells, fibrous fluoro-edenite behaved similarly to the unrelated asbestos type crocidolite, whose connection with severe inflammation and cancer of the lung is renowned.

In plain English

This laboratory study exposed A549 cells to fibrous fluoro-edenite. A549 is a cell line from a human lung carcinoma with properties of the cells lining the lung's air sacs. Fluoro-edenite is a mineral from Biancavilla, Sicily, where an unusual cluster of malignant mesothelioma had been reported. The fibers averaged 15.5 micrometres long and 0.45 micrometres in diameter. Crocidolite asbestos was tested alongside as a positive control. Reported results used 20 micrograms per square centimetre of fluoro-edenite and 4 of crocidolite, over 24 to 72 hours. Fluoro-edenite disrupted the cells' actin structure and made cells flatten, spread and enlarge. It caused a time-dependent rise in the share of cells with several nuclei, though this was greater with crocidolite. Both fibers reduced the number of viable cells. Neither fiber induced apoptosis (programmed cell death) or significantly altered the cell cycle. Fluoro-edenite increased release of the inflammatory signals IL-6 and IL-8 from 48 hours; crocidolite caused more IL-6. The authors concluded the fiber behaved similarly to crocidolite in these cells. They added that more work is needed to show a direct link to cancer.

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: in vitro cell culture experiment, with crocidolite asbestos as a positive control
• Who was studied: A549 cells, a human lung carcinoma cell line with properties of alveolar (type-II like) epithelial cells; no people or animals were studied
• Exposure: Fibrous fluoro-edenite from Biancavilla (average length 15.5 micrometres, average diameter 0.45 micrometres) at 10, 20 and 40 micrograms per square centimetre. NIOSH standard crocidolite (about 1 micrometre diameter, 25 micrometres length) at 2, 4 and 10 micrograms per square centimetre. Exposures lasted 24, 48 and 72 hours. Only the 20 (fluoro-edenite) and 4 (crocidolite) doses were reported in the results.
• Main results:
  • In fluoro-edenite-treated cells, the actin stress fibers seen in control cells disappeared and membrane ruffles appeared. Cells flattened, spread and increased greatly in size. This was evident after 48 hours and more so at 72 hours; with crocidolite the effects appeared already at 24 hours.
  • Fibrous fluoro-edenite, like crocidolite, caused a time-dependent increase in the percentage of multinucleated cells. The increase was greater in crocidolite-treated cells. The figures were given only in a graph.
  • From the first 24 hours, fibrous fluoro-edenite caused a dramatic decrease in the number of viable cells, comparable to crocidolite. The figures were given only in a graph.
  • Neither crocidolite nor fluoro-edenite induced apoptosis, measured by annexin staining after 72 hours. Levels of the Bcl-2, Bcl-XL and Bax proteins were comparable in untreated and treated cells. The authors reported that p53 expression was not influenced (data not shown).
  • Neither fiber significantly altered passage of cells through the cell cycle. For example, at 72 hours the percentage of cells in G0/G1 phase was 54.35 in controls, 54.05 with crocidolite and 53.81 with fibrous fluoro-edenite.
  • Fluoro-edenite fibers increased the amounts of IL-6 and IL-8 secreted by the cells from 48 hours of exposure. The results were comparable to crocidolite, which promoted a more consistent secretion of IL-6. The figures were given only in graphs.
• The authors' conclusion: The authors concluded that in lung epithelial cells fibrous fluoro-edenite behaved similarly to crocidolite. They proposed, as a hypothesis, that multinucleated cells continuing to divide and ongoing cytokine release could contribute to cancer. They stated that additional work is required to demonstrate a direct link between fibrous fluoro-edenite exposure and cancer development.
• Limitations the authors state:
  • The authors acknowledged possible problems arising from A549 cells already having a transformed (cancer) phenotype.
  • The authors stated that several aspects of fibrous fluoro-edenite's toxicity to cells remain to be defined.
  • The authors stated that additional work is required to demonstrate a direct link between fibrous fluoro-edenite exposure and cancer.

Topics

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

Medical terms in this study, explained in our Lexicon: Cytokine, fluoro-edenite, A549 Cells, Malignant Mesothelioma, Biancavilla, Amphibole Group, Mesothelioma, Crocidolite.

Related studies

• Effects of the new-identified amphibole fluoro-edenite in lung epithelial cells — S. Travaglione, B. Bruni, et al. (2003)
• Inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells — M.M. Acencio, B. Soares, et al. (2015)
• Mineral fibre toxicity: expression of retinoblastoma (Rb) and phospho-retinoblastoma (pRb) protein in alveolar epithelial and mesothelial cell lines exposed to fluoro-edenite fibres — G. Musumeci, V. Cardile, et al. (2011)
• Fluoro-edenite fibers induce expression of Hsp70 and inflammatory response — V. Cardile, L. Lombardo, et al. (2007)
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