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Increasing Surface Iron Increases Asbestos-Induced Expression of Procollagen and Transforms Nonfibrogenic Titanium Dioxide Into a Fibrogenic Dust^*

Role of NF-B

^* 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

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-ß₁ (TGFß₁), and platelet-derived growth factor (PDGF)-A. Expression of tumor necrosis factor-, PDGF-B, and TGF 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, TGFß, and PDGF-A expression. Incubation of the explants with MG-132, a proteasome inhibitor that prevents NF-B activation, returned expression of Procol to control values, but did not affect expression of TGFß 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-B.

Footnotes

Abbreviations: AOS = active oxygen species; PDGF = platelet-derived growth factor; TGFß = transforming growth factor-ß; TNF- = tumor necrosis factor-

Supported by Medical Research Council; Canada.

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This Article Full Text (PDF) Free Submit a response View responses Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Churg, A. Articles by Wright, J. L. Search for Related Content PubMed Articles by Churg, A. Articles by Wright, J. L.