Adenovirus-mediated transfer and overexpression of heme oxygenase 1 cDNA in lungs attenuates elastase-induced pulmonary emphysema in mice.
Adenovirus-mediated transfer and overexpression of heme oxygenase 1 cDNA in lungs attenuates elastase-induced pulmonary emphysema in mice.
复制标题
DOI：
10.1089/hum.2005.16.318
复制
发表时间：
2005-04
影响因子：
4.2
通讯作者：
T. Shinohara;T. Kaneko;Y. Nagashima;A. Ueda;A. Tagawa;Y. Ishigatsubo
中科院分区：
文献类型：
--
作者：
T. Shinohara;T. Kaneko;Y. Nagashima;A. Ueda;A. Tagawa;Y. Ishigatsubo
血红素加氧酶1（HO-1）是一种诱导酶，催化血红素生成胆红素、铁蛋白和一氧化碳。由于HO-1的表达增强提供了抗炎作用并赋予细胞保护，我们研究了通过在肺中接种编码HO-1的腺病毒（Ad.HO-1）诱导的HO-1过表达是否会预防猪胰弹性蛋白酶（PPE）诱导的肺气肿。用HO-1腺病毒（Ad.HO-1）预处理肺组织，使肺组织中HO-1的表达上调，可减轻PPE引起的支气管肺泡灌洗液（BALF）中性粒细胞增多和肺泡扩大。它还降低了PPE诱导的肿瘤坏死因子α、白细胞介素（IL）-6和角质形成细胞衍生趋化因子水平升高，并增加了BALF中抗炎细胞因子IL-10的水平。这些结果表明，Ad.HO-1诱导的HO-1过表达抑制PPE诱导的肺气肿，通过调节小鼠肺中的细胞因子和趋化因子谱来减轻嗜酸性炎症。
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.