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1 McDonald Research Laboratory and iCAPTURE Center, University of British Columbia, Vancouver, British Columbia V6Z 1Y6; and 2 Environmental Health Directorate, Health Canada, Ottawa, Ontario K1A 0L2, Canada
We examined the
hypothesis that ambient particulate matter with a diameter of <10 µm
(PM10)-induced lung inflammation is amplified by latent
adenovirus infection. Inflammatory mediator expression in response to
PM10 exposure was compared between adenovirus
E1A-transfected A549 alveolar epithelial cells and cells transfected
with control plasmid. Messenger RNA was measured by the RNase
protection assay and protein by ELISA or immunocytochemistry.
Intercellular adhesion molecule-1 and IL-8 mRNA and protein were
increased in E1A-positive cells exposed to 500 µg/ml
PM10. Monocyte chemoattractant protein-1 mRNA and protein
were unchanged in E1A-positive cells but increased in E1A-negative
cells after 100 and 500 µg/ml PM10 exposure.
Electrophoretic mobility shift assays showed increased NF-
B and
decreased specificity protein 1 nuclear binding in E1A-positive cells
exposed to PM10. These results indicate that E1A modulates
cytokine and adhesion molecule expression in epithelial cells in a
manner that could amplify PM10-induced lung inflammation.
We suggest that this amplified inflammatory response may contribute to
the pathogenesis of exacerbations of chronic obstructive pulmonary
disease associated with exposure to particulate matter air pollution.
interleukin-8; monocyte chemoattractant protein-1; intercellular
adhesion molecule-1; nuclear factor-
B; transcription factor
specificity protein 1; particulate matter
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