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Air Pollution Particles Produce Airway Wall Remodeling in Rat Tracheal Explants

Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; and Health Canada, Ottawa, Ontario, Canada

Address correspondence to: Andrew Churg, M.D., Department of Pathology, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5 Canada. E-mail: achurg{at}interchange.ubc.ca

There is evidence that chronic exposure to high levels of ambient particulate pollutants (PM) is associated with chronic airflow obstruction, but how this occurs is not known. We exposed rat tracheal explants to Ottawa urban air particles (ECH93) or diesel exhaust particles. After 7 d in air organ culture, both types of PM increased explant procollagen and transforming growth factor (TGF)-ß₁ gene expression, and markedly increased tissue hydroxyproline. For both types of particle, nuclear factor-B inhibitor SN50 completely blocked increased gene expression. With EHC93, procollagen expression was inhibited by the oxidant scavenger, tetramethylthiourea, and by the iron chelator, deferoxamine, but TGF-ß₁ expression was not inhibited by deferoxamine. Inhibitors of extracellular signal regulated kinase and p38 kinase did not affect EHC93-induced gene expression. With diesel exhaust particles, tetramethylthiourea and deferoxamine had no effect, but extracellular signal regulated kinase and p38 inhibitors completely blocked effects on procollagen and TGF-ß₁. Fetuin, an inhibitor of TGF-ß receptor binding, prevented increases in procollagen gene expression. We conclude that two common types of PM can directly induce expression of genes involved in fibrogenesis and actual airway wall fibrosis through nuclear factor-B– and TGF-ß–mediated mechanisms. PM-induced airway wall remodeling may play an important role in producing airflow obstruction in individuals living in high PM regions.

Abbreviations: diesel exhaust particles, DEP • deferoxamine, DFX • Ottawa urban air particles, EHC93 • extracellular signal related kinase, ERK • nuclear factor-B, NF-B • ambient particulate air pollutants, PM • transforming growth factor-ß, TGF-ß • tetramethylthiourea, TMTU

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