Heme oxygenase-1 expression in human lungs with cystic fibrosis and cytoprotective effects against Pseudomonas aeruginosa in vitro.
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.
Zhou
Hailan
H
Department of Pediatrics, University of Florida, Gainesville, Florida 32610, USA.
Lu
Fuhua
F
Latham
Christopher
C
Zander
Dani S
DS
Visner
Gary A
GA
D017209:Apoptosis / Q000276:immunology*; D002460:Cell Line; D003550:Cystic Fibrosis / Q000150:complications / Q000201:enzymology* / Q000276:immunology* / Q000382:microbiology; D019610:Cytoprotection / Q000276:immunology; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000276:immunology; D051547:Heme Oxygenase-1; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000201:enzymology* / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology; D008565:Membrane Proteins; D018384:Oxidative Stress / Q000276:immunology; D011552:Pseudomonas Infections / Q000150:complications / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1