Change of heme oxygenase-1 expression in lung injury induced by chrysotile asbestos in vivo and in vitro

Our plain-English summary of Change of heme oxygenase-1 expression in lung injury induced by chrysotile asbestos in vivo and in vitro, by H. Nagatomo, Y. Morimoto, A. Ogami, et al (Inhalation Toxicology, 2007).

The study

• Authors: H. Nagatomo, Y. Morimoto, A. Ogami, M. Hirohashi, T. Oyabu, K. Kuroda, T. Higashi, I. Tanaka
• Journal: Inhalation Toxicology
• Published: 2007;19(4):317-23
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Oxidative stress is thought to be the pathogenesis of pulmonary fibrosis induced by asbestos, and heme oxygenase-1 (HO-1) protects lung tissue against oxidative stress. We hypothesized that HO-1 is also associated with oxidative lung injury caused by exposure to chrysotile asbestos. This study was conducted to investigate the HO-1 expression of lungs in lung injury by chrysotile asbestos in vivo and in vitro. Male Wistar rats were administered 1 mg or 2 mg chrysotile suspended in saline by a single intratracheal instillation and were sacrificed at 3 days, 1 wk, 1 mo, 3 mo, and 6 mo of recovery time. The expression of HO-1 was observed by Western blot analysis, reverse-transcription polymerase chain reaction, and immunostaining. Protein levels of HO-1 increased at from 3 days to 6 mo following intratracheal instillation of 1 or 2 mg chrysotile. The mRNA levels of HO-1 increased at 3 mo and 6 mo following intratracheal instillation of 1 or 2 mg chrysotile. HO-1-positive cells were mainly found in the alveolar macrophages during immunostaining. We then examined HO-1 protein expression in human alveolar epithelial cells (A549). A549 cells were incubated with chrysotile at concentrations of 0, 12.5, 25, 50, and 100 microg/ml over 24 h. Increased expression of HO-1 protein was found following exposure to 25 or 50 microg/ml of chrysotile. Increased expression of HO-1 was also found at 6, 12, 24, and 48 h after exposure to 50 microg/ml of chrysotile with a peak at 24 h. These findings suggest that HO-1 is related to lung injury arising from exposure to chrysotile asbestos in vivo and in vitro.

In plain English

This laboratory study examined whether chrysotile asbestos changes levels of heme oxygenase-1 (HO-1), a protein thought to protect lungs against oxidative stress. Male Wistar rats received one dose of 1 mg or 2 mg Canadian chrysotile into the windpipe (intratracheal instillation). They were examined 3 days to 6 months later, five animals per group. Saline and titanium dioxide were used for comparison. Lung HO-1 protein rose significantly from 3 days to 6 months after 1 mg and was raised throughout after 2 mg. HO-1 messenger RNA rose significantly only at 3 and 6 months. The authors saw no remarkable difference between doses. Six months after 2 mg, HO-1 staining was mainly in alveolar macrophages, and lungs showed inflammatory cells and partial granulomatous lesions. In human lung cells (A549, a cell line originally derived from an alveolar-cell carcinoma), HO-1 protein rose significantly after 24 hours at 25 and 50 micrograms per millilitre of chrysotile. At 50, it peaked at 24 hours in a separate time-course experiment. The authors suggested that HO-1 is regulated as an antioxidative defense factor in chrysotile-caused lung injury.

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: Animal experiment (rats given chrysotile into the windpipe) combined with a laboratory cell-culture experiment
• Who was studied: Male Wistar rats, 10 weeks old, from Kyudo (Kumamoto, Japan). For each exposure category there were 5 exposed and 5 control animals, examined at 3 days, 1 week, 1 month, 3 months and 6 months. The cell experiments used human alveolar epithelial cells (A549), a line originally derived from an individual with alveolar-cell carcinoma.
• Exposure: Canadian chrysotile class 7M, given once into the windpipe at 1 mg or 2 mg in 0.4 ml saline. Comparison rats received saline, or titanium dioxide (1 mg or 2 mg) as a negative control. The A549 cells were exposed to chrysotile at 0, 12.5, 25, 50 and 100 micrograms per millilitre for 24 hours, and to 50 micrograms per millilitre for 0 to 48 hours.
• Main results:
  • In rats given 1 mg chrysotile, lung HO-1 protein increased significantly from 3 days to 6 months. In the 2 mg group, HO-1 protein was increased during the entire experimental period, and the difference was more significant at 1 month to 6 months.
  • In rats, HO-1 messenger RNA increased significantly at 3 months and 6 months after 1 mg or 2 mg chrysotile. There were no changes at 3 days and 1 month.
  • The authors reported no remarkable dose dependency between the 1 mg and 2 mg groups.
  • Immunostaining was done only on rats given 2 mg chrysotile, 6 months after exposure. These lungs showed intensive HO-1 staining, mainly in alveolar macrophages, compared with the saline and titanium dioxide groups. Some alveolar and bronchial epithelial cells also stained positive.
  • Six months after 2 mg chrysotile, rat lungs showed infiltration of inflammatory cells and partial granulomatous lesions. HO-1-positive cells were found around the granulomatous lesions but not inside them.
  • In A549 cells exposed for 24 hours, HO-1 protein increased significantly at 25 and 50 micrograms per millilitre of chrysotile. The article does not report a significant increase at 12.5 or 100.
  • In a separate time-course experiment, A549 cells exposed to 50 micrograms per millilitre of chrysotile showed increased HO-1 protein at 6, 12, 24 and 48 hours, with a peak at 24 hours. Cells exposed to titanium dioxide showed no change at 24 hours.
• The authors' conclusion: Based on the increases in HO-1 they observed after chrysotile exposure, the authors suggested that HO-1 is regulated as an antioxidative defense factor in lung injury caused by chrysotile asbestos. They measured HO-1 levels and did not test whether HO-1 protected the lung.

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, Oxidative Stress, Pulmonary Fibrosis, Alveolar Macrophage, A549 Cells.

Related studies

• Expression of heme oxygenase-1 in the lungs of rats exposed to crocidolite asbestos — H. Nagatomo, Y. Morimoto, et al. (2005)
• Expression of heme oxygenase-1 in the lungs of rats exposed to potassium octatitanate whiskers — Y. Obata, Y. Morimoto, et al. (2011)
• Chrysotile asbestos causes AEC apoptosis via the caspase activation in vitro and in vivo — T. Kido, Y. Morimoto, et al. (2008)
• Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1 — C. Loreto, R. Caltabiano, et al. (2020)
• Heme oxygenase-1 in environmental toxin-induced lung disease — M.L. Wu, M.D. Layne, et al. (2012)
• Calcitonin gene-related peptide (CGRP) as hazard marker for lung injury induced by dusts — Y. Morimoto, A. Ogami, et al. (2007)

Browse more research in Inhalation Toxicology, or return to medical research.