Adenovirus-mediated transfer and overexpression of heme oxygenase 1 cDNA in lungs attenuates elastase-induced pulmonary emphysema in mice.
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.
Shinohara
Takeshi
T
Department of Internal Medicine and Clinical Immunology, Yokohama City University School of Medicine, Kanazawa, Yokohama, Kanagawa 236-0004, Japan.
Kaneko
Takeshi
T
Nagashima
Yoji
Y
Ueda
Atsuhisa
A
Tagawa
Akihiro
A
Ishigatsubo
Yoshiaki
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism* / Q000627:therapeutic use*; D051547:Heme Oxygenase-1; D006652:Histological Techniques; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D010196:Pancreatic Elastase / Q000633:toxicity*; D011656:Pulmonary Emphysema / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018076:DNA, Complementary; D015850:Interleukin-6; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D010196:Pancreatic Elastase