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Inflammatory Response in Airway Epithelial Cells Isolated from Patients with Cystic Fibrosis

Departments of Pediatrics and Internal Medicine, Washington University School of Medicine, St. Louis, Missouri; and Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa

Correspondence and requests for reprints should be addressed to Dwight Look, M.D., University of Iowa College of Medicine, Department of Internal Medicine, C33A-GH, 200 Hawkins Drive, Iowa City, IA 52242. E-mail: dwight-look{at}uiowa.edu

The concept that inflammatory gene expression is dysregulated in airway epithelial cells from patients with cystic fibrosis (CF) is controversial. To examine this possibility systematically, responses to inflammatory stimuli were compared in CF airway epithelial cell lines without versus with wild-type CF transmembrane conductance regulator (CFTR) complementation and in tracheobronchial epithelial cells from patients with versus without CF. Epithelial cell expression of the leukocyte adhesion glycoprotein intercellular adhesion molecule-1 (ICAM-1) and release of the neutrophil chemoattractant interleukin (IL)-8 were determined under basal conditions or after exposure to stimuli important in CF airway inflammatory responses. We found that uncorrected CF airway epithelial cell lines inconsistently expressed higher ICAM-1 and IL-8 levels. Human CF tracheobronchial epithelial cells in primary culture released moderately increased IL-8 only after exposure to Pseudomonas aeruginosa. In CF cells with higher IL-8 release, transient expression of wild-type CFTR using an adenoviral vector did not specifically affect cytokine levels. The results indicate that there is considerable variability in airway epithelial cell responses to inflammatory stimuli among different individuals and cell models systems. Although increased ICAM-1 and IL-8 expression are observed in some CF airway epithelial cell models, many CF cells do not exhibit significant dysregulation of these important inflammatory genes.

Key Words: adenoviral vector • Haemophilus influenzae • intercellular adhesion molecule-1 • interleukin-8 • Pseudomonas aeruginosa

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