Inflammatory mediator mRNA expression by adenovirus E1A-transfected bronchial epithelial cells

Yuji Higashimoto, W. Mark Elliott, Ali Reza Behzad, Edward G. Sedgwick, Tatsuo Takei, James C. Hogg, Shizu Hayashi*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    45 Scopus citations

    Abstract

    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-KB binding activity of nuclear extracts in E1A transfectants than controls. E1A-positive transfectants constitutively expressed transforming growth factor-β1 mRNA and protein, whereas this expression was either very low or not detected in control cells. We conclude that adenoviral E1A tranfection transforms primary HBE cells and upregulates their production of mediators that are clinically relevant to the pathogenesis of chronic obstructive pulmonary disease.

    Original languageEnglish (US)
    Pages (from-to)200-207
    Number of pages8
    JournalAmerican Journal of Respiratory and Critical Care Medicine
    Volume166
    Issue number2
    DOIs
    StatePublished - Jul 15 2002

    Keywords

    • Adenovirus E1A proteins
    • Intercellular adhesion molecule-1
    • Interleukin-8
    • Lipopolysaccharides
    • Transforming growth factor-β

    ASJC Scopus subject areas

    • Pulmonary and Respiratory Medicine
    • Critical Care and Intensive Care Medicine

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