Adenoviral E1A modulates inflammatory mediator expression by lung epithelial cells exposed to PM10.
We examined the hypothesis that ambient particulate matter with a diameter of <10 microm (PM(10))-induced lung inflammation is amplified by latent adenovirus infection. Inflammatory mediator expression in response to PM(10) 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 microg/ml PM(10). Monocyte chemoattractant protein-1 mRNA and protein were unchanged in E1A-positive cells but increased in E1A-negative cells after 100 and 500 microg/ml PM(10) exposure. Electrophoretic mobility shift assays showed increased NF-kappaB and decreased specificity protein 1 nuclear binding in E1A-positive cells exposed to PM(10). These results indicate that E1A modulates cytokine and adhesion molecule expression in epithelial cells in a manner that could amplify PM(10)-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.
Fujii
Takeshi
T
McDonald Research Laboratory and iCAPTURE Center, University of British Columbia, St. Paul's Hospital, 1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada.
Hogg
James C
JC
Keicho
Naoto
N
Vincent
Renaud
R
Van Eeden
Stephan F
SF
Hayashi
Shizu
S
D017500:Adenovirus E1A Proteins / Q000502:physiology*; D000397:Air Pollution; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010316:Particle Size; D012333:RNA, Messenger / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
D017500:Adenovirus E1A Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D018799:Intercellular Adhesion Molecule-1