Inflammatory mediator mRNA expression by adenovirus E1A-transfected bronchial epithelial cells.
Lung tissue from patients with emphysema and airway obstruction carries excess adenoviral E1A DNA that is expressed as protein in airway surface epithelium and is associated with an increased inflammatory response. To examine mechanisms by which latent adenoviral infection might amplify the inflammatory process, we transfected primary human bronchial epithelial (HBE) cells from three separate patients undergoing lung resection so that they stably expressed adenovirus E1A. Lipopolysaccharide stimulation of the E1A-transfected HBE cells increased intercellular adhesion molecule-1 and interleukin-8 mRNA and protein expression compared with control cells from the same patient. It also induced greater intercellular adhesion molecule-1 promoter activity and greater nuclear factor-kappa B binding activity of nuclear extracts in E1A transfectants than controls. E1A-positive transfectants constitutively expressed transforming growth factor-beta 1 mRNA and protein, whereas this expression was either very low or not detected in control cells. We conclude that adenoviral E1A transfection transforms primary HBE cells and upregulates their production of mediators that are clinically relevant to the pathogenesis of chronic obstructive pulmonary disease.
University of British Columbia, McDonald Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Yuji
Y
Higashimoto
W Mark
WM
Elliott
Ali R
AR
Behzad
Edward G
EG
Sedgwick
Tatsuo
T
Takei
James C
JC
Hogg
Shizu
S
Hayashi
D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000378:metabolism; D000258:Adenovirus Infections, Human / Q000378:metabolism*; D000368:Aged; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D017500:Adenovirus E1A Proteins; D018836:Inflammation Mediators; D016209:Interleukin-8; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D018799:Intercellular Adhesion Molecule-1