Chrysotile asbestos causes AEC apoptosis via the caspase activation in vitro and in vivo

Our plain-English summary of Chrysotile asbestos causes AEC apoptosis via the caspase activation in vitro and in vivo, by T. Kido, Y. Morimoto, E. Asonuma, et al (Inhalation Toxicology, 2008).

The study

• Authors: T. Kido, Y. Morimoto, E. Asonuma, K. Yatera, A. Ogami, T. Oyabu, I. Tanaka, M. Kido
• Journal: Inhalation Toxicology
• Published: 2008;20(3):339-47
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

To determine whether alveolar epithelial cell (AEC) apoptosis via caspase activation is involved in asbestos-induced lung injury, we examined apoptosis, caspase-3 and-9 activation using chrysotile asbestos exposure models in vitro and in vivo. Apoptotic cells were assessed in A549 cells with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method after 48 hours exposure of chrysotile asbestos (5 to 100 ug/cm2). Asbestos exposure induced a dose-dependent increase of apoptotic cells, and both pretreatment with Z-LEHD-FMK (caspase-3 inhibitor) or Z-DEMK-FMK (caspase-9 inhibitor) significantly suppressed asbestos-induced apoptosis. Expression of cleaved caspase-3 and-9 increased significantly from 18 to at least 48 hours after asbestos exposure. In vivo study, either 1 or 2 mg of chrysotile asbestos were administered into rat lungs intratracheally, and the lungs were obtained 3 days, 1 and 2 weeks, 1, 3 and 6 months after the administration. Asbestos exposure increased the number of apoptotic cells and the activation of cleaved caspase-3 and -9 most at 3 days in a dose dependent manner, and continued to increase them until at least 6 months after asbestos exposure. Apoptotic cells and cleaved caspase-3 and -9 positive cells were mainly observed in AECs. These findings suggest that AEC apoptosis via caspase-3 and -9 activation is involved in asbestos-induced lung injury.

In plain English

This laboratory study used cultured human lung cells and rats. The authors exposed A549 cells, an immortalized human alveolar epithelial (air-sac lining) cell line, to chrysotile asbestos at 5 to 100 µg/cm2 for 48 hours. Chrysotile increased apoptosis (programmed cell death) in a dose-dependent way, peaking at 50 µg/cm2. At 100 µg/cm2, apoptosis and caspase activation were lower than at 50. Caspase inhibitors given beforehand significantly reduced this cell death, and activated caspase-3 and -9 plateaued between 18 and 48 hours. Male Wistar rats received 1 or 2 mg of chrysotile into the windpipe (5 exposed and 5 control rats per exposure category). In these rats, apoptosis and caspase activation peaked at 3 days and remained increased for at least 6 months. Apoptotic cells were found in alveolar epithelial cells and also in granulomatous tissue, vessel walls and beneath the pleura. The measured amounts of cell death and caspase activation appear only in figures, not as numbers. The authors concluded that asbestos induced alveolar epithelial cell apoptosis through caspase activation. They speculated this is a crucial factor in diseases such as asbestosis.

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 study: in vitro experiments on a human cell line and an in vivo animal experiment in rats
• Who was studied: In vitro: A549 immortalized human alveolar epithelial cell line. In vivo: male Wistar rats, 10 weeks old, from Kyudo (Kumamoto, Japan); 5 exposed and 5 control rats for each exposure category; examined at 3 days, 1 week, 2 weeks, 1 month, 3 months and 6 months after instillation
• Exposure: In vitro: UICC chrysotile B asbestos at 5 to 100 µg/cm2 for 48 hours. In vivo: Canadian chrysotile class 7M given as a single intratracheal instillation of 1 or 2 mg in 0.4 ml saline; controls received saline
• Main results:
  • In A549 cells, chrysotile caused a significant dose-dependent increase in TUNEL-positive (apoptotic) cells compared with controls, peaking at 50 µg/cm2
  • In A549 cells, pretreatment with 1 or 2 µM of the caspase-3 or caspase-9 inhibitor significantly reduced the number of apoptotic cells compared with untreated groups
  • In A549 cells, cleaved (activated) caspase-3 and -9 increased and reached a plateau between 18 and 48 hours after exposure
  • In A549 cells, apoptosis and caspase activation were lower at 100 µg/cm2 than at 50 µg/cm2; the authors suggested higher concentrations may shift cell death from apoptosis to necrosis
  • In rats, inflammatory cell infiltration and granulomatous response were seen 3 days after instillation, mainly in alveolar airspaces and terminal airways, and decreased over time
  • In rats, apoptotic cells increased most at 3 days and remained increased until at least 6 months after exposure
  • In rats given 1 or 2 mg, activated caspase-3 and -9 increased most at 3 days and remained increased until at least 6 months
  • In rats, apoptotic cells were found in alveolar epithelial cells and also in granulomatous response, vascular walls and the subpleural area
• The authors' conclusion: The authors concluded that asbestos induced alveolar epithelial cell apoptosis via caspase activation in vitro and in vivo. They speculated that this is a crucial causing factor of inflammatory and fibrotic lung diseases such as asbestosis.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Lake Asbestos of Quebec, Black Lake, Quebec

All asbestos mines

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Apoptosis, Asbestos Exposure, A549 Cells.

Related studies

• Asbestos causes apoptosis in alveolar epithelial cells: role of iron-induced free radicals — A. Aljandali, H. Pollack, et al. (2001)
• Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation — Y.J. Lee, Y.J. Lee, et al. (2015)
• Chrysotile Causes Human Bronchial Epithelial Cell Apoptosis in Response to the Fas-Mediated Apoptosis Pathway — M. Zhang, J. Chen, et al. (2017)
• Change of heme oxygenase-1 expression in lung injury induced by chrysotile asbestos in vivo and in vitro — H. Nagatomo, Y. Morimoto, et al. (2007)
• P53 mediates amosite asbestos-induced alveolar epithelial cell mitochondria-regulated apoptosis — V. Panduri, S. Surapureddi, et al. (2006)
• Forsterite exposure causes less oxidative DNA damage and lung injury than chrysotile exposure in rats — A. Takata, H. Yamauchi, et al. (2009)

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