Adenovirus-mediated transfer and overexpression of heme oxygenase 1 cDNA in lungs attenuates elastase-induced pulmonary emphysema in mice

Hum Gene Ther. 2005 Mar;16(3):318-27. doi: 10.1089/hum.2005.16.318.


Heme oxygenase 1 (HO-1) is an inducible enzyme that catalyzes heme to generate bilirubin, ferritin, and carbon monoxide. Because enhanced expression of HO-1 provides an anti-inflammatory effect and confers cytoprotection, we examined whether HO-1 overexpression induced by inoculation of mice with an adenovirus encoding HO-1 (Ad.HO-1) in the lung would prevent pulmonary emphysema induced by porcine pancreatic elastase (PPE). Pretreatment with Ad.HO-1, which upregulated production of HO-1 in the lung, attenuated the PPE-induced increase of neutrophils in bronchoalveolar lavage fluid (BALF) and enlargement of alveoli. It also reduced PPE-induced elevated levels of tumor necrosis factor alpha, interleukin (IL)-6, and keratinocyte-derived chemokine, and increased the level of anti-inflammatory cytokine IL-10 in BALF. These results suggest that Ad.HO-1-induced HO-1 overexpression suppressed PPE-induced emphysema by attenuating neutrophilic inflammation via modulating cytokine and chemokine profiles in mouse lungs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid / chemistry
  • DNA, Complementary / genetics
  • Gene Expression / drug effects
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Genetic Vectors / pharmacology
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Heme Oxygenase (Decyclizing) / therapeutic use*
  • Heme Oxygenase-1
  • Histological Techniques
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Membrane Proteins
  • Mice
  • Neutrophils / metabolism
  • Pancreatic Elastase / toxicity*
  • Pulmonary Emphysema / chemically induced*
  • Pulmonary Emphysema / pathology
  • Pulmonary Emphysema / therapy*
  • Tumor Necrosis Factor-alpha / metabolism


  • DNA, Complementary
  • Interleukin-6
  • Membrane Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Pancreatic Elastase