Adenovirus E1A gene dysregulates ICAM-1 expression in transformed pulmonary epithelial cells
| Autor: | Shizu Hayashi, James C. Hogg, Naoto Keicho, W M. Elliott |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Lipopolysaccharides
Pulmonary and Respiratory Medicine Genes Viral viruses CD14 Clinical Biochemistry Stimulation Biology Transfection Epithelium Interferon-gamma Plasmid Tumor Cells Cultured medicine Humans RNA Messenger Lung Molecular Biology Gene Cell Line Transformed Regulation of gene expression Dose-Response Relationship Drug Tumor Necrosis Factor-alpha Cell Biology Intercellular Adhesion Molecule-1 Molecular biology Kinetics Blood medicine.anatomical_structure Gene Expression Regulation Cell culture Adenovirus E1A Proteins |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 16:23-30 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/ajrcmb.16.1.8998075 |
| Popis: | Previous studies from our laboratory demonstrated that adenovirus E1A DNA and proteins are detected in lungs of patients with chronic obstructive pulmonary disease (COPD). Since adenovirus E1A gene products are known to regulate the expression of many genes by interacting with cellular transcription factors, we postulate that E1A enhances the production of inflammatory mediators and exacerbates the inflammatory process in smokers' lungs. To examine this possibility, we transfected A549 human pulmonary epithelial cells with a plasmid carrying the adenoviral E1A gene and isolated stable transfectants expressing E1A proteins. These E1A-producing clones were tested for intercellular adhesion molecule-1 (ICAM-1) expression. As compared with parental cells or cells transfected with control plasmid, ICAM-1 expression was suppressed after IFN-gamma stimulation but markedly increased by LPS stimulation of E1A-positive cells. This LPS-mediated ICAM-1 induction was serum-dependent but the LPS receptor, CD14, was not detected on the surface of the E1A transfectants. We conclude that E1A proteins modulate ICAM-1 induction by inflammatory stimuli and render lung epithelial cells sensitive to LPS, and suggest that dysregulation of inflammatory mediator expression by adenoviral E1A could amplify the inflammatory process present in airways of smokers to produce COPD. |
| Databáze: | OpenAIRE |
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