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Heme Oxygenase-1 Expression in Human Lungs with Cystic Fibrosis and Cytoprotective Effects against Pseudomonas Aeruginosa In Vitro

Departments of Pediatrics, University of Florida, Gainesville, Florida; and Department of Pathology, University of Texas Medical School at Houston, Houston, Texas

Correspondence and requests for reprints should be addressed to Gary A. Visner, D.O., University of Florida, Department of Pediatrics, P.O. Box 100296, Gainesville, FL 32610. E-mail: visnega{at}peds.ufl.edu

Inflammation and oxidative stress play important roles in cystic fibrosis (CF) lung disease. Inflammatory/oxidant-mediated induction of heme oxygenase-1 (HO-1) is believed to be a cytoprotective response. This study examined HO-1 expression in lung samples from patients with CF using immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. In addition, we evaluated myeloperoxidase staining as a marker of acute inflammation and potentially an increase in oxidant stress and Prussian blue and ferritin staining to assess iron status of the lung. Macrophage HO-1 staining was increased in diseased lungs as compared with normal control subjects and correlated with myeloperoxidase staining. Quantitative reverse transcription-polymerase chain reaction further supported an increase in HO-1 expression in CF lung disease. Although iron staining was minimal, ferritin staining was increased in diseased lungs in concert with HO-1 staining. To determine whether HO-1 induction was cytoprotective, we evaluated a CF airway epithelial cell line, IB3.1, in response to Pseudomonas aeruginosa–induced injury/apoptosis in cells overexpressing HO-1 by either transient or stable transfection of pcDNA3.1/HO-1 construct. Overexpression of HO-1 resulted in protection against P. aeruginosa–induced injury/apoptosis. This suggests that the induction of HO-1 in patients with CF is a cytoprotective event and that augmenting its expression is a potential therapy against bacterial injury.

Key Words: chronic airway disease • heme oxygenase-1 • inflammation • oxidative stress • Pseudomonas aeruginosa

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