Adenovirus-Mediated Transfer and Overexpression of Heme Oxygenase 1 cDNA in Lungs Attenuates Elastase-Induced Pulmonary Emphysema in Mice
- 1 March 2005
- journal article
- research article
- Published by Mary Ann Liebert Inc in Human Gene Therapy
- Vol. 16 (3) , 318-327
- https://doi.org/10.1089/hum.2005.16.318
Abstract
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 α, interleukin (IL)-6, and keratinocytederived 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.Keywords
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