Articles |

Increasing Surface Iron Increases Asbestos-Induced Expression of Procollagen and Transforms Nonfibrogenic Titanium Dioxide Into a Fibrogenic Dust*: Role of NF-κB FREE TO VIEW

A. Churg, MD; J. Dai; J. L. Wright, MD
Author and Funding Information

*From the Department of Pathology, University of British Columbia, Vancouver, BC.

Correspondence to: Andrew Churg, MD, Department of Pathology, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5

Chest. 2001;120(1_suppl):S19. doi:10.1378/chest.120.1_suppl.S19
Text Size: A A A
Published online

It is generally accepted that asbestos produces active oxygen species (AOS) in tissue and induces inflammatory and fibrogenic mediators and matrix components, but the relationship of AOS and these mediators/matrix is unclear. To examine the role of AOS, we loaded asbestos fibers with increasing amounts of iron(II)/iron(III) and applied the fibers to rat tracheal explants. After 7 days in air organ culture, explants were analyzed for gene expression by reverse transcription-polymerase chain reaction. Increasing amounts of surface iron were associated with increasing expression of procollagen type I (Procol), transforming growth factor-β1 (TGFβ1), and platelet-derived growth factor (PDGF)-A. Expression of tumor necrosis factor-α, PDGF-B, and TGFα was not affected by asbestos alone or by iron-loaded asbestos. Treatment of asbestos fibers with the iron chelator deferoxamine completely abolished the increases in Procol, TGFβ, and PDGF-A expression. Incubation of the explants with MG-132, a proteasome inhibitor that prevents NF-κB activation, returned expression of Procol to control values, but did not affect expression of TGFβ or PDGF-A. Addition of iron to 0.1 μ titanium dioxide, a particle that ordinarily does not induce expression of procollagen in this system, also increased Procol expression. These findings indicate that particle surface iron and, by implication, AOS can induce fibrogenic mediators and matrix components not only with “fibrogenic” dusts, such as asbestos, but with theoretically nonfibrogenic particles, such as air pollutant particles, if they contain redox-active iron. For procollagen, this process appears to be mediated by activation of NF-κB.

Abbreviations: AOS = active oxygen species; PDGF = platelet-derived growth factor; TGFβ = transforming growth factor-β; TNF-α = tumor necrosis factor-α

Supported by Medical Research Council; Canada.




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543