Cellular and molecular mechanisms of asbestos-induced fibrosis

Our plain-English summary of Cellular and molecular mechanisms of asbestos-induced fibrosis, by R. Robledo, B. Mossman (Journal of Cellular Physiology, 1999).

The study

• Authors: R. Robledo, B. Mossman
• Journal: Journal of Cellular Physiology
• Published: 1999;180(2):158-66
• Type of article: Review
• Cited by: 92 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Pleural and pulmonary fibrosis (asbestosis) are ramifications of occupational exposures to asbestos fibers, a diverse family of ubiquitous, naturally-occurring minerals. The pathogenesis of asbestos-associated fibrosis involves the participation of a number of cell types and is characterized by an early and persistent inflammatory response that involves the generation of oxidants, growth factors, chemokines, and cytokines. These mediators may also contribute directly to cell injury, proliferation, and fibrogenesis. After interaction with cells, asbestos fibers trigger a number of signaling cascades involving mitogen-activated protein kinases (MAPK) and nuclear factor kappa-B (NF-kappaB). Activation of transcription factors such as NF-kappaB and activator protein-1 (AP-1) may be linked to increases in early response genes (e.g., c-jun and c-fos) which govern proliferation, apoptosis, and inflammatory changes in the cells of the lung. The goal of this article is to review the cellular and molecular mechanisms of asbestos-induced fibrosis that may be critical to the development of effective treatment regimens.

In plain English

This article was a review, not a new study. The authors summarized published research on how asbestos fibers cause scarring of the lung (asbestosis) and pleura. The research came from cell culture experiments, animal studies and some human studies. They noted that most of the research they described used chrysotile and crocidolite asbestos. Rodent studies they reviewed indicated that short asbestos fibers were less potent than long, thin fibers in starting key cell responses. The review described three processes: iron-rich fibers such as crocidolite producing oxidants; an inflammatory response involving immune cells and chemical messengers such as TNF; and signaling pathways that switch on genes linked to cell growth, cell death and inflammation. The authors stated that the responses of lung lining (epithelial) cells were pivotal. They also cited rodent studies in which catalase or phytic acid significantly reduced crocidolite-induced inflammation and fibrosis. The authors concluded that alveolar macrophages and neutrophils may be key to starting and maintaining inflammation, and that asbestosis probably involves multiple mechanisms. They cautioned against applying results from these models directly to human disease.

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 published research on the cellular and molecular mechanisms of asbestos-induced fibrosis
• Who was studied: No study population of its own. The review drew on published in vitro (cell culture) studies, experimental animal studies (mainly rats and mice, plus a sheep model) and human studies.
• Exposure: Asbestos fibers in general. The article names six types (chrysotile, crocidolite, amosite, tremolite, anthophyllite, actinolite), and most of the research it describes used chrysotile and crocidolite.
• Main results:
  • Summarizing rodent studies by others, the authors stated that short asbestos fibers are less potent than long, thin fibers in starting key cellular responses linked to disease.
  • The review described iron-rich fibers, such as crocidolite, generating oxidants directly through chemical reactions on the fiber surface.
  • Citing a study in mice, the review reported that mice lacking TNF receptors and exposed to chrysotile asbestos did not develop the fibroproliferative lesions seen in normal mice.
  • Citing a human study, the review reported that three TGF-beta isoforms were upregulated in the fibrotic lungs of chrysotile asbestos workers.
  • From the studies reviewed, the authors concluded that responses of lung epithelial cells are pivotal to the development of asbestosis.
  • The review described asbestos fibers activating cell signaling pathways, including ERK phosphorylation and activity in mesothelial cells.
  • Citing rodent studies, the authors reported that giving catalase or phytic acid (an iron chelator) significantly inhibited crocidolite-induced inflammation and fibrosis.
• The authors' conclusion: The authors concluded that alveolar macrophages and neutrophils may be key to starting and maintaining inflammation. They also concluded that asbestosis is a complicated series of events that probably involves multiple mechanisms and crosstalk between messengers and cell types.
• Limitations the authors state:
  • The authors cautioned that results from animal and post-mortem models may not apply directly to human asbestosis.
  • The authors stated that it is difficult to work out which fiber properties matter for toxicity.
  • The authors noted that some of the signaling pathways they described had not been thoroughly investigated in animal models of asbestosis.

Topics

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

Medical terms in this study, explained in our Lexicon: Fibrosis, Pulmonary Fibrosis, Occupational Exposure, Cytokine, Apoptosis.

Related studies

• Cellular mechanisms of reactive oxygen metabolite generation from human polymorphonuclear leukocytes induced by crocidolite asbestos — T. Ishizaki, E. Yano, et al. (1997)
• Gene expression profiles reveal increased mClca3 (Gob5) expression and mucin production in a murine model of asbestos-induced fibrogenesis — T. Sabo-Attwood, M. Ramos-Nino, et al. (2005)
• Susceptibility to asbestos-induced and transforming growth factor-beta1-induced fibroproliferative lung disease in two strains of mice — G.S. Warshamana, D.A. Pociask, et al. (2002)
• The latent form of TGFbeta(1) is induced by TNFalpha through an ERK specific pathway and is activated by asbestos-derived reactive oxygen species in vitro and in vivo — D.E. Sullivan, M. Ferris, et al. (2008)
• Similar and Differential Canonical Pathways and Biological Processes Associated With Multiwalled Carbon Nanotube and Asbestos-Induced Pulmonary Fibrosis: A 1-Year Postexposure Study — J.M. Dymacek, B.N. Snyder-Talkington, et al. (2018)
• Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)

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