Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 166, Issue 2, Pages 101-110Publisher
ACADEMIC PRESS INC
DOI: 10.1006/taap.2000.8957
Keywords
PM10; NF-kappa B; I kappa B; iron; A549 cells; endotoxin
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Exposure to particulate air pollution (PM10) is associated with exacerbations of respiratory diseases and increased cardiopulmonary mortality. PM10 induces lung inflammation in rats, which has been attributed to many factors, including the ultrafine components of PM10, endotoxins, and transition metals. In this study, we investigated in alveolar epithelial (A549) cells whether PM10 could activate nuclear factor-kappa B (NF-kappa B), a transcription factor stimulated in response to many proinflammatory agents. Our results show that PM10 samples from various sites within the United Kingdom cause nuclear translocation, DNA-binding, and transcriptional activation of NF-kappa B in A549 cells. Furthermore, increased NF-kappa B activity was observed in the absence of I kappa B degradation. To evaluate the role of iron, A549 cells were exposed to PM10 previously treated with phosphate-buffered saline (PBS), deferoxamine mesylate, or deferoxamine plus ferrozine. PBS-treated and, to a lesser extent, deferoxamine-treated PM10 were able to activate NF-kappa B, whereas this response was completely abrogated in cells exposed to PM10 treated with both deferoxamine and ferrozine. Moreover, we studied the effects of soluble components of PM10 on NF-kappa B activation by exposing alveolar epithelial cells to soluble fractions from PM10 treated with PBS or the metal chelators. We found that, compared with fractions from PBS-treated PM10 which activated NF-kappa B, fractions from PM10 treated with deferoxamine and ferrozine did not stimulate NF-kappa B activity above background levels. Coincubation of polymixin B, an endotoxin-binding compound, and PR10 did not inhibit NF-kappa B. In summary, PM10 activates NF-kappa B in A549 cells by an iron-mediated mechanism in the absence of I kappa B degradation. (C) 2000 Academic Press.
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