Pseudomonas aeruginosa-induced neutrophilic lung inflammation is attenuated by adenovirus-mediated transfer of the heme oxygenase 1 cDNA in mice.
Heme oxygenase (HO) is well known as the rate-limiting enzyme in the oxidative degradation of heme to biliverdin, carbon monoxide (CO), and iron. Based on recent evidence that overexpression of HO-1 confers protection against various types of cell and tissue injury by regulating apoptotic cell death or cytokine expression profiles, the present study was performed to examine whether the transfer of exogenous HO-1 cDNA in the lung would provide therapeutic effect in a murine model of lung inflammation induced by Pseudomonas aeruginosa. HO-1 overexpression clearly attenuated neutrophil influx and decreased numbers of apoptotic bronchial epithelial cells. Interestingly, the overexpression of Bcl-2, a known antiapoptotic factor, was observed and thought to be the mechanism that inhibits bronchial epithelial cellular apoptosis. It is thus suggested that HO-1 overexpression is useful for treating P. aeruginosa-associated lung inflammation by attenuating neutrophil influx and apoptotic cell death.
Tsuburai
Takahiro
T
First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama City 236-0004, Japan.
Kaneko
Takeshi
T
Nagashima
Yoji
Y
Ueda
Atsuhisa
A
Tagawa
Akihiro
A
Shinohara
Takeshi
T
Ishigatsubo
Yoshiaki
Y
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics* / Q000378:metabolism; D051547:Heme Oxygenase-1; D007120:Immunochemistry; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D011552:Pseudomonas Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011550:Pseudomonas aeruginosa
D016207:Cytokines; D018076:DNA, Complementary; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse