Adenovirus, particularly its E1A protein, has been investigated in the pathogenesis of chronic obstructive pulmonary disease (COPD). High levels of E1A DNA were found in the lungs of COPD patients, where its expression increased with disease severity. In lung epithelial cells, E1A increased intercellular adhesion molecule-1 and interleukin-8 expression, as well as nuclear factor-kappaB activation, in response to inflammatory stimuli. In addition to regulating the mediators that promote emphysema, E1A upregulates transforming growth factor-beta1 expression in bronchiolar epithelial cells and transforms lung epithelial cells to express mesenchymal markers. These results support its additional role in the airway remodeling process reported in COPD.