Occupational lung disease and the role of peptide growth factors

Our plain-English summary of Occupational lung disease and the role of peptide growth factors, by A.R. Brody (Current Opinion in Pulmonary Medicine, 1997).

The study

• Author: A.R. Brody
• Journal: Current Opinion in Pulmonary Medicine
• Published: 1997;3(3):203-8
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Occupational lung disease can take many forms, including obstructive airway disease, asthma, and restrictive parenchymal fibrosis. It would not be useful to attempt an all-encompassing review of such a broad topic, even if one were restricted to the most recent literature. Thus, I have chosen a small corner of one disease process that relates to work ongoing in my laboratory, ie, the potential role of growth factors in the pathogenesis of fibroproliferative lung disease. This process is the cornerstone of interstitial pulmonary fibrosis, which is caused by inhaling such commonly used materials as asbestos and silica. Diffuse interstitial pulmonary fibrosis results from chronic exposures in the workplace, and the initial lesions of the fibroproliferative process that culminate in interstitial pulmonary fibrosis are readily produced in the laboratory by exposing rats and mice. The disease could be mediated by a combination of peptide growth factors and cytokines that are expressed at sites of lung injury.

In plain English

This article was a short narrative review, mainly of earlier rat and mouse experiments from the author's own laboratory, though it also presented some recent results. The author focused on how peptide growth factors might drive fibroproliferative lung disease, the scarring behind interstitial pulmonary fibrosis linked to inhaled asbestos and silica. In cited cell studies, asbestos fibers raised alpha-type receptors for platelet-derived growth factor (PDGF) on cultured rat lung fibroblasts about 5-fold and led the cells to release PDGF-A. In rats exposed to roughly 1000 fibers per cubic centimetre for 5 hours, PDGF and transforming growth factor-alpha appeared at developing lung lesions for about 2 weeks. The cited laboratory papers name the fiber as chrysotile asbestos. The author's most recent experiments showed dexamethasone increasing PDGF alpha-receptor expression in rat lung fibroblasts. Unpublished observations showed that mice lacking TNF-alpha receptors were protected from asbestos-induced fibrosis. The author concluded that numerous growth factors are expressed at sites of lung injury. The author added that which factors drive the disease had yet to be defined, and called the proposed scenario too simple.

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, centred on the author's own laboratory's animal and cell-culture studies of growth factors in fibroproliferative lung disease. It also includes some recent laboratory experiments (dexamethasone, Figure 1) and unpublished observations.
• Who was studied: No human population was studied. The work reviewed used rats and mice exposed to asbestos, and rat lung cells (fibroblasts, macrophages) grown in the laboratory.
• Exposure: Asbestos fibers. The cited laboratory papers name chrysotile asbestos. In the rat inhalation model, animals were exposed to about 1000 fibers/cm³ for 5 hours. Iron- and air-exposed animals served as controls in the TGF-alpha study. In the recent cell experiments, the exposure was dexamethasone.
• Main results:
  • In a cited laboratory study (Bonner et al.), adding asbestos fibers alone to cultured rat lung fibroblasts raised expression of the alpha-type PDGF receptor, with about 5-fold increases in cell surface receptors.
  • In a cited parallel study (Lasky et al.), asbestos treatment caused the lung mesenchymal cells to release their own PDGF-A.
  • In a cited study of asbestos-exposed rats (Liu et al.), PDGF-A and -B mRNA was found at the developing lung lesions immediately after the 5-hour exposure and for about 2 weeks afterward. It was found mainly in bronchiolar-alveolar epithelium, macrophages and some interstitial cells.
  • In a cited study of asbestos-exposed rats (Liu et al.), TGF-alpha was expressed within 24 hours. Its gene expression and protein stayed significantly higher than in iron- and air-exposed control animals for 2 weeks.
  • In the author's most recent experiments (Figure 1), dexamethasone increased PDGF alpha-receptor mRNA expression and receptor protein in rat lung fibroblasts.
  • The author reported unpublished observations that mice with the receptors for TNF-alpha knocked out were protected from the fibrogenic effects of inhaled asbestos fibers.
• The authors' conclusion: The author concluded that numerous growth factors are expressed at sites of lung injury. The author also concluded that the findings support the idea that PDGF plays a role in the development of asbestos-induced fibrogenic lesions.
• Limitations the authors state:
  • Which growth factor or factors actually mediate these responses had not yet been defined.
  • Whether the receptor-upregulation mechanism seen in cultured cells operates in living animals after asbestos exposure or corticosteroid treatment was an open question.
  • The author described the proposed sequence of events as too simple.

Topics

Medical terms in this study, explained in our Lexicon: Occupational Lung Disease, Parenchymal Fibrosis, Interstitial, Pulmonary Fibrosis, Cytokine.

Related studies

• Up-regulated expression of transforming growth factor-alpha in the bronchiolar-alveolar duct regions of asbestos-exposed rats — J.Y. Liu, G.F. Morris, et al. (1996)
• Role of peptide growth factors in asbestos-related human lung cancer — B. Guillemin, Y. Zhang, et al. (1991)
• Differential proliferation of rat lung fibroblasts induced by the platelet-derived growth factor-AA, -AB, and -BB isoforms secreted by rat alveolar macrophages — J.C. Bonner, A.R. Osornio-Vargas, et al. (1991)
• Rat pleural mesothelial cells adapted to serum-free medium as a model for the study of growth factor effects — E. Bermudez, B. Libbus, et al. (1998)
• Primary lung fibroblasts from the 129 mouse strain exhibit reduced growth factor responsiveness in vitro — D.M. Brass, S.Y. Tsai, et al. (2001)
• Chrysotile asbestos upregulates gene expression and production of alpha-receptors for platelet-derived growth factor (PDGF-AA) on rat lung fibroblasts — J.C. Bonner, A.L. Goodell, et al. (1993)

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