ADENOVIRUS E1A GENP, DYSREGULATES ICAM-1 EXPRESSION IN TRANSFORMED PULMONARY EPITHELIAL-CELLS

Previous studies from our laboratory demonstrated that adenovirus E1A DNA and proteins are detected in lungs of patients with chronic obstru ctive pulmonary disease (COPD). Since adenovirus E1A gene products are known to regulate the expression of many genes by interacting with ce llular transcription factors, we postulate that E1A enhances the produ ction of inflammatory mediators and exacerbates the inflammatory proce ss in smokers' lungs. To examine this possibility, we transfected A549 human pulmonary epithelial cells with a plasmid carrying the adenovir al E1A gene and isolated stable transfectants expressing E1A proteins. These E1A-producing clones were tested for intercellular adhesion mol ecule-1 (ICAM-1) expression. As compared with parental cells or cells transfected with control plasmid, ICAM-1 expression was suppressed aft er IFN-gamma stimulation but markedly increased by LPS stimulation of E1A-positive cells. This LPS-mediated ICAM-1 induction was serum-depen dent but the LPS receptor, CD14, was not detected on the surface of th e E1A transfectants. We conclude that E1A proteins modulate ICAM-1 ind uction by inflammatory stimuli and render lung epithelial cells sensit ive to LPS, and suggest that dysregulation of inflammatory mediator ex pression by adenoviral E1A could amplify the inflammatory process pres ent in airways of smokers to produce COPD.