Mineral dusts directly induce epithelial and interstitial fibrogenic mediators and matrix components in the airway wall

Our plain-English summary of Mineral dusts directly induce epithelial and interstitial fibrogenic mediators and matrix components in the airway wall, by J. Dai, B. Gilks, K. Price, et al (American Journal of Respiratory and Critical Care Medicine, 1998).

The study

• Authors: J. Dai, B. Gilks, K. Price, A. Churg
• Journal: American Journal of Respiratory and Critical Care Medicine
• Published: 1998;158(6):1907-13
• Cited by: 47 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Exposure to mineral dusts is associated with the development of chronic airflow obstruction, probably mediated in part by dust-induced fibrosis of the small airways. To investigate the mechanism of fibrosis, we exposed rat tracheal explants to amosite asbestos, iron oxide, or titanium dioxide. Explants were then maintained in air organ culture, and the expression of genes encoding for various mediators and matrix components assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). At 7 d, all dusts produced significant increases in platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta1 (TGF-beta1) gene expression compared with control; asbestos and titanium dioxide produced increases in PDGF-B, and titanium dioxide increased TGF-alpha expression. Only asbestos caused increases in procollagen expression. No dust increased expression of tumor necrosis factor-alpha (TNF-alpha), fibronectin, or tropoelastin. Elevations in these factors coincided temporally with transport of particles into the epithelium and then to the subepithelial space. By in situ hybridization, TGF-beta gene expression was found in both the epithelium and subepithelial (interstitial) space, and PDGF-B and procollagen gene expression in the subepithelial space. Chemical analysis showed a small increase in hydroxyproline, a measure of collagen content, in asbestos-treated explants. We conclude that mineral dusts can induce airway wall fibrosis by directly upregulating proliferative and fibrogenic mediators as well as matrix components in the airway epithelium and interstitium, and that neither airspace nor circulating inflammatory cells are required for these effects. Different mineral dusts produce different patterns of reaction.

In plain English

This laboratory study used rat windpipe pieces (tracheal explants) grown in culture. The authors bathed explants for one hour in amosite asbestos, iron oxide or titanium dioxide, or medium alone (controls). Gene activity for growth factors and matrix components was measured at 1, 3 and 7 days (titanium dioxide: 3 and 7 days only). No differences from controls were seen at 1 and 3 days, except a very slight (about 10%) fibronectin drop after asbestos at day 3. At 7 days all three dusts raised PDGF-A and TGF-beta1 gene activity. Only amosite raised procollagen type I (a collagen building block) gene activity, by about 35%. Only amosite raised collagen content (hydroxyproline), by 15% (p = 0.05, one-tailed test). More iron oxide and titanium dioxide aggregates than asbestos fibers passed through the lining into deeper tissue. The authors concluded that dusts can directly trigger fibrosis-related changes in the airway wall without inflammatory cells from airspaces or blood, and that dusts differ in their effects. They noted the trachea takes up dust more slowly than the deeper lung.

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 experiment on rat tracheal explants in organ culture (animal tissue studied outside the body)
• Who was studied: Tracheal explants (about 2 by 2 mm) from 250-g male Sprague-Dawley rats. Explants from several animals were mixed, 3 explants were pooled per data point, and each test group had three data points.
• Exposure: UICC amosite asbestos standard reference sample, iron oxide (hematite) and titanium dioxide (anatase). Explants were submerged for 1 hour in a 5 mg/ml dust suspension and then cultured. Asbestos and iron oxide explants were examined at 1, 3 and 7 days, and titanium dioxide explants at 3 and 7 days only. Controls were exposed to culture medium only.
• Main results:
  • Asbestos and iron oxide were tested first. Because no effects were seen at 1 or 3 days with those dusts, titanium dioxide was tested only at 3 and 7 days.
  • The authors reported no differences between dust-exposed and control explants at 1 and 3 days of culture for any dust. The exception was the slight fibronectin decrease after asbestos reported below.
  • Amosite asbestos at 7 days: about 60% increase in PDGF-A chain, 30% in PDGF-B chain, 35% in procollagen type I and 25% in TGF-beta1 gene expression compared with control
  • Iron oxide at 7 days: 30% increase in PDGF-A and 75% increase in TGF-beta1 gene expression, with no increase in PDGF-B or procollagen
  • Titanium dioxide at 7 days: 40% increase in PDGF-A, 35% in PDGF-B, 100% in TGF-beta and 140% in TGF-alpha gene expression, with no increase in procollagen. The authors reported all these differences as statistically significant (p less than 0.01 or less).
  • TNF-alpha expression did not differ from controls. Fibronectin was very slightly decreased (about 10%) at 3 and 7 days after asbestos only; the article does not state whether this decrease was statistically significant. No tropoelastin signal was found in any group.
  • Hydroxyproline (collagen content) at 7 days: 15% increase in asbestos-exposed explants (p = 0.05, one-tailed test). Iron- and titanium-exposed explants did not differ from control.
  • No particles were in the subepithelial tissue at 24 hours. Numbers rose by 7 days. More iron oxide and titanium dioxide 'particles' reached this tissue than amosite fibers; the authors note these counted 'particles' are actually aggregates of finer particles. At 7 days the subepithelial counts per mm of epithelium were 18 (asbestos fibers), 65 (iron oxide) and 110 (titanium dioxide).
  • By in situ hybridization at 7 days, TGF-beta1 expression appeared in both the epithelium and the subepithelial space, while procollagen was seen only in the subepithelial space. There were no obvious differences in signal distribution between dust-exposed and control explants.
• The authors' conclusion: The authors concluded that dusts have the intrinsic property of inducing cell proliferation, cytokine secretion and fibrosis in the airway wall, that airway wall fibrosis may occur without airspace or circulating inflammatory cells, and that different dusts evoke different patterns of response.
• Limitations the authors state:
  • Dust uptake is much slower in the trachea than in the distal lung, and lower than in monolayer cell cultures. Respiratory bronchioles, the main site of dust deposition and fibrosis in life, appear to take up more dust.
  • The low dust uptake probably explains the relatively small increases observed. Bulk analysis of explants dilutes products with non-producing cells, so the results should not be read as absolute increases in mediator expression.

Topics

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

Medical terms in this study, explained in our Lexicon: Interstitial, Fibrogenic, Obstructive Lung Disease, Fibrosis, Amosite, Platelet-Derived Growth Factor (PDGF), Tumor Necrosis Factor-alpha (TNF-α), Epithelium.

Related studies

• Airway wall remodeling induced by occupational mineral dusts and air pollutant particles — A. Churg, J.L. Wright (2002)
• Iron enhances uptake of mineral particles and increases lipid peroxidation in tracheal epithelial cells — B. Keeling, K.Y. Li, et al. (1994)
• Distinctive profile of alveolar macrophage-derived cytokine release induced by fibrogenic and nonfibrogenic mineral dusts — I. Lemaire, S. Ouellet (1996)
• Effects of cigarette smoke on epithelial uptake of non-asbestos mineral particles in tracheal organ culture — B. Keeling, J. Hobson, et al. (1993)
• Accumulation of mixed mineral dusts in the lungs of rats during chronic inhalation exposure — C.H. McMillan, A.D. Jones, et al. (1989)
• Small airways disease and mineral dust exposure. Prevalence, structure, and function — A. Churg, J.L. Wright, et al. (1985)

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