Latent adenoviral infection induces production of growth factors relevant to airway remodeling in COPD

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 286; no. 1; pp. 189 - L197
• Main Authors: Ogawa, Emiko, Elliott, W. Mark, Hughes, Fiona, Eichholtz, Thomas J, Hogg, James C, Hayashi, Shizu
• Format: Journal Article
• Language: English
• Published: United States 01.01.2004
• Subjects: Adenovirus E1A Proteins - genetics; Adenovirus E1B Proteins - genetics; Adenovirus Infections, Human - complications; Adenovirus Infections, Human - physiopathology; Bronchi - cytology; Cell Differentiation; Connective Tissue Growth Factor; Culture Media; Epithelial Cells - cytology; Epithelial Cells - physiology; Epithelial Cells - virology; Humans; Immediate-Early Proteins - genetics; Intercellular Signaling Peptides and Proteins - genetics; Phenotype; Pulmonary Disease, Chronic Obstructive - physiopathology; Pulmonary Disease, Chronic Obstructive - virology; Respiratory Mucosa - cytology; RNA, Messenger - analysis; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta1
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00315.2002

1 McDonald Research Laboratories-iCAPTURE Centre, Department of Pathology and Laboratory Medicine, St. Paul's Hospital-Providence Health Care, University of British Columbia, Vancouver, British Columbia, Canada V6Z 1Y6; and 2 RA Biology and 3 Asthma Disease Biology, GlaxoSmithKline R&D, Stevenage SG1 2NY, United Kingdom Submitted 17 September 2002 ; accepted in final form 22 September 2003 Previous studies showed an association between latent adenoviral infection with expression of the adenoviral E1A gene and chronic obstructive pulmonary disease (COPD). The present study focuses on how the adenoviral E1A gene could alter expression of growth factors by human bronchial epithelial (HBE) cells. The data show that connective tissue growth factor (CTGF) and transforming growth factor (TGF)- 1 mRNA and protein expression were upregulated in E1A-positive HBE cells. Upregulation of CTGF in this in vitro model was independent of TGF- secreted into the growth medium. Comparison of E1A-positive with E1A-negative HBE cells showed that both expressed cytokeratin but only E1A-positive cells expressed the mesenchymal markers vimentin and -smooth muscle actin. We conclude that latent infection of epithelial cells by adenovirus E1A could contribute to airway remodeling in COPD by the viral E1A gene, inducing TGF- 1 and CTGF expression and shifting cells to a more mesenchymal phenotype. bronchial epithelial cell; differentiation; transforming growth factor- ; connective tissue growth factor; chronic obstructive pulmonary disease Address for reprint requests and other correspondence: E. Ogawa, UBC McDonald Research Laboratories-The iCAPTURE Centre, St. Paul's Hospital, 1081 Burrard St., Vancouver, BC, Canada V6Z 1Y6 (E-mail: eogawa{at}kuhp.kyoto-u.ac.jp ).