Fluoro-edenite fibers induce expression of Hsp70 and inflammatory response

Our plain-English summary of Fluoro-edenite fibers induce expression of Hsp70 and inflammatory response, by V. Cardile, L. Lombardo, E. Belluso, et al (International Journal of Environmental Research and Public Health, 2007).

The study

• Authors: V. Cardile, L. Lombardo, E. Belluso, A. Panico, M. Renis, A. Gianfagna, M. Balazy
• Journal: International Journal of Environmental Research and Public Health
• Published: 2007;4(3):195-202
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Many asbestos-like mineral fibers have been detected in the air of mountainous and volcanic areas of Italy and other parts of the world. These fibers have been suspected to be the cause of increased incidences of lung cancer and other lung diseases in these areas. However, the mechanisms of the cellular response and defense following exposure to these microscopic fibers have not been characterized. We continue to study these mechanisms to be able to propose preventive strategies in large populations. The objective of the present study was to determine comparatively biological responses of mesothelial Met-5A and monocyte-macrophage J774 cells following exposure to two types of fluoro-edenite fibers having low and high iron content (labeled 19 and 27, respectively) obtained from Biancavilla (Sicily, Italy). The reference fiber was a non-iron fibrous tremolite from Val di Susa (Piemonte, Italy). The cells were treated with 5, 50, and 100 mug of fibrous matter per 1 ml for 72 hr. We identified several key mechanisms by which cells responded and counteracted the injury induced by these fibers. The fibers caused induction of the heat shock protein 70 (Hsp70), stimulated formation of reactive oxygen species (detected by using DCFH-DA as a fluorescent probe) and NO* (measured as nitrite). Exposure of cells to the fibers induced lactate dehydrogenase activity and decreased viability. The fluoro-endenite type 27 was the most potent fiber tested, which indicated that iron and possibly manganese contribute significantly to this fiber toxicity. The J774 cells were more sensitive to fluoro-edenite than Met-5A cells suggesting that the primary site of the fiber-induced inflammatory response could be the macrophage rather than the pulmonary epithelium. Fluoro-edenite produces more biological alterations with respect to non-iron tremolite. Hsp70 and free radicals could be important factors in the context of mineral fiber-induced acute lung injury leading possibly to mutagenic effects. We anticipate that pharmacological blockade of the fiber-dependent cellular responses could in long term offer preventive approach to combat lung diseases induced by these fibers.

In plain English

This was a laboratory study on cells grown in dishes, not a study of people. The authors exposed human mesothelial cells (Met-5A) and mouse monocyte-macrophage cells (J774) to two fluoro-edenite fibers from Biancavilla, Sicily: one with lower iron content (labelled 19) and one with higher iron content (labelled 27). For comparison they used a non-iron fibrous tremolite from Val di Susa, Piedmont. Cells received 5, 50 or 100 micrograms of fiber per millilitre for 72 hours. Both fluoro-edenites raised levels of a stress protein, Hsp70, in both cell lines even at the lowest dose. Tremolite at 100 micrograms per millilitre had about the same effect as fluoro-edenite at 5. The fibers also increased nitrite (a marker of nitric oxide), reactive oxygen species and release of the enzyme LDH, a sign of cell damage, and they reduced cell viability. The macrophage cells reacted more strongly than the mesothelial cells in Hsp70 and nitrite. The authors concluded that fluoro-edenite produced more biological changes than tremolite, and that iron and possibly manganese contribute to its toxicity.

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 laboratory experiment on cultured cell lines
• Who was studied: Two cell lines: Met-5A human non-malignant transformed mesothelial cells and J774 mouse monocyte-macrophage cells; results are means of three experiments performed in triplicate
• Exposure: Fluoro-edenite fibers from Biancavilla, Sicily, with low (type 19) and high (type 27) iron content, and non-iron fibrous tremolite from Val di Susa, Piedmont, as reference. Doses were 5, 50 and 100 micrograms per millilitre for 72 hours. All fibers averaged 30 micrometres long and 5 micrometres in diameter.
• Main results:
  • Fluoro-edenite caused Hsp70 induction in both cell lines at concentrations as low as 5 micrograms per millilitre after 72 hours
  • J774 macrophage cells were more sensitive than Met-5A mesothelial cells in terms of Hsp70 induction
  • Tremolite was less effective at inducing Hsp70. Tremolite at 100 micrograms per millilitre had a similar effect to fluoro-edenite at 5 micrograms per millilitre.
  • Nitrite levels increased significantly and with concentration in both cell lines
  • In J774 cells, fluoro-edenite, particularly the low-iron form 19, had a strong effect on nitric oxide formation compared with Met-5A cells
  • High-iron fluoro-edenite 27 at 5 micrograms per millilitre strongly stimulated reactive oxygen species in J774 cells. Met-5A cells were stimulated by all three fiber types.
  • Fluoro-edenite stimulated LDH release, a marker of cell death and membrane breakdown
  • Viability of both cell lines fell significantly after fluoro-edenite at 5 micrograms per millilitre. Tremolite was inactive at that concentration.
  • At higher concentrations, fluoro-edenite 19 was more potent than the other particles in reducing viability
• The authors' conclusion: The authors concluded that fluoro-edenite produces more biological alterations than non-iron tremolite. They said iron and possibly manganese contribute significantly to its toxicity, and that Hsp70 and free radicals could be important factors in fiber-induced acute lung injury, possibly leading to mutagenic effects.

Topics

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

Medical terms in this study, explained in our Lexicon: fluoro-edenite, Mineral Fiber, Lung Cancer, Macrophage, Biancavilla, Tremolite, Reactive Oxygen Species (ROS), Lactate Dehydrogenase (LDH).

Related studies

• 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)
• Immunohistochemical expression of retinoblastoma and phospho-retinoblastoma protein in sheep lung exposed to fluoro-edenite fibers — G. Musumeci, C. Loreto, et al. (2010)
• Multinucleation and pro-inflammatory cytokine release promoted by fibrous fluoro-edenite in lung epithelial A549 cells — S. Travaglione, B.M. Bruni, et al. (2006)
• Behaviour of the new asbestos amphibole fluor-edenite in different lung cell systems — V. Cardile, M. Renis, et al. (2004)
• Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report — G. Angelico, R. Caltabiano, et al. (2018)
• Angiogenesis correlates with macrophage and mast cell infiltration in lung tissue of animals exposed to fluoro-edenite fibers — G. Musumeci, C. Loreto, et al. (2016)

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