Heme oxygenase-1 in environmental toxin-induced lung disease

Our plain-English summary of Heme oxygenase-1 in environmental toxin-induced lung disease, by M.L. Wu, M.D. Layne, S.F. Yet (Toxicology Mechanisms and Methods, 2012).

The study

• Authors: M.L. Wu, M.D. Layne, S.F. Yet
• Journal: Toxicology Mechanisms and Methods
• Published: 2012;22(5):323-9
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In the US, lung disease is the number three killer and accounts for one of every six deaths. Furthermore, more than 35 million US populations are now living with a chronic lung disease. Therefore, it is of urgent need to develop novel strategies that can protect against the development and progression of lung disease. Inhalation of air pollutants or environmental toxins induces inflammation and oxidative stress in the lung, resulting in tissue damage with subsequent decline in lung function. Heme oxygenase-1 (HO-1) is a stress response protein, which is highly inducible in response to pathological stimulation. Due to the cumulative effects of HO-1 on heme catabolism and the generation of biologically active downstream products, induction of HO-1 might serve as a protective mechanism against oxidative stress and inflammation-induced injury. Accumulating evidences have indicated a protective function of HO-1 against lung injury. This review highlights the roles of HO-1 in lung disease induced by environmental toxins such as cigarette smoke (CS), silica, and asbestos.

In plain English

This article was a review of research on heme oxygenase-1 (HO-1), a protein that cells make under stress, in lung disease caused by cigarette smoke, silica and asbestos. It also briefly reported one experiment by the authors. Normal mice and mice lacking HO-1 breathed room air or cigarette smoke for 6 months. After smoke exposure, a measure of airspace size used as an indicator of emphysema was significantly higher in the mice lacking HO-1. On asbestos, the review summarized laboratory and animal studies by other researchers, not by the authors. Those studies reported that Libby six-mix, a mixture of vermiculite from mines in Libby, Montana, increased reactive oxygen species and HO-1 gene expression in human mesothelial cells. Libby amphibole and amosite increased HO-1 gene expression in human airway cells. Crocidolite increased HO-1 in rat lungs at 1 mg and 2 mg doses, and chrysotile gave similar results. The authors noted that how asbestos injures the lung is not well understood. They concluded that HO-1 plays important roles in the response to asbestos-induced oxidative stress and lung injury, and that its protective role in asbestosis needs further investigation.

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: Narrative review of laboratory, animal and human studies by other researchers, plus one brief mouse experiment by the authors (cigarette smoke exposure in normal and HO-1 knockout mice)
• Who was studied: Reviewed studies used cells, animals and people. The authors' own experiment used wild type mice and HO-1 knockout mice exposed to room air or cigarette smoke for 6 months
• Exposure: Cigarette smoke, silica, and asbestos. The asbestos studies reviewed involved Libby six-mix vermiculite, Libby amphibole, amosite, crocidolite and chrysotile
• Main results:
  • Authors' own mouse experiment: after cigarette smoke exposure, mean linear intercept (an indicator of pulmonary emphysema) was significantly higher in HO-1 knockout mice than in wild type mice (p less than 0.05). There was no difference between the two types of mice on room air
  • Reviewed study (Hillegass et al. 2010): Libby six-mix increased reactive oxygen species production in mesothelial cells, and the increase depended on dose
  • Reviewed study (Hillegass et al. 2010): HO-1 mRNA (gene expression) was significantly induced in human mesothelial cells exposed to Libby six-mix
  • Reviewed study (Duncan et al. 2010): the respirable size fraction of Libby amphibole and of amosite increased HO-1 mRNA expression in primary human airway epithelial cells
  • Reviewed study (Duncan et al. 2010): unfractionated amosite and Libby amphibole also increased HO-1 mRNA expression
  • Reviewed study (Nagatomo et al. 2005): in rats, a low dose of crocidolite asbestos (1 mg) increased HO-1 expression from 1 week up to 3 months
  • Reviewed study (Nagatomo et al. 2005): in rats, a higher dose of crocidolite (2 mg) increased HO-1 protein levels from day 3 until 6 months
  • Reviewed study (Nagatomo et al. 2007): chrysotile exposure, in cells and in animals, gave results similar to crocidolite
  • Reviewed study (Hevel et al. 2008): in crocidolite-treated A549 human lung epithelial cells, the Nrf2-mediated oxidative stress pathway played a major role in the gene changes caused by crocidolite
• The authors' conclusion: The authors concluded that the reviewed results indicate HO-1 plays important roles in the response to asbestos-induced oxidative stress and lung injury, and that further investigation of its protective role in asbestosis is warranted
• Limitations the authors state:
  • The authors noted that the mechanisms by which asbestos injures the lung are not well understood

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Oxidative Stress.

Related studies

• 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)
• Expression of heme oxygenase-1 in the lungs of rats exposed to potassium octatitanate whiskers — Y. Obata, Y. Morimoto, et al. (2011)
• Expression of heme oxygenase-1 in the lungs of rats exposed to crocidolite asbestos — H. Nagatomo, Y. Morimoto, et al. (2005)
• Heme oxygenase-1 promoter polymorphism is associated with risk of malignant mesothelioma — A. Murakami, Y. Fujimori, et al. (2012)
• 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)
• The role of iron in Libby amphibole-induced acute lung injury and inflammation — J.H. Shannahan, A.J. Ghio, et al. (2011)

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