Heme Oxygenase-1 in Cystic Fibrosis and Cytoprotective Effects Against Pseudomonas aeruginosa

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 RT-PCR. 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 to normal controls, and correlated with myeloperoxidase staining. Quantitative RT-PCR 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 if HO-1 induction was cytoprotective, we evaluated a CF airway epithelial cell line, IB3.1, in response to Pseudomonas aeruginosainduced 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 Pseudomonas aeruginosainduced 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.