Regulation of heme oxygenase-1 expression in vivo and in vitro in hyperoxic lung injury
Regulation of heme oxygenase-1 expression in vivo and in vitro in hyperoxic lung injury
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DOI：
10.1165/ajrcmb.14.6.8652184
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发表时间：
1996-06-01
影响因子：
6.4
通讯作者：
Choi, AMK
中科院分区：
文献类型：
--
作者：
Lee, PJ;Alam, J;Choi, AMK
使用高氧作为大鼠氧化剂引起的肺损伤模型，我们探索了体内和体外血红素加氧酶-1 (HO-1) 表达的调节。我们证明高氧后大鼠肺部 HO-1 信使核糖核酸 (mRNA) 水平显着增加。 HO-1 mRNA 表达增加与 HO-1 蛋白和酶活性增加相关。高氧后大鼠肺的免疫组织化学研究表明，多种细胞类型中 HO-1 的表达增加，包括支气管肺泡上皮、间质细胞和炎症细胞。然后，我们在体外检查了高氧后 HO-1 表达的调节，并观察到各种培养细胞（包括上皮细胞、成纤维细胞、巨噬细胞和平滑肌细胞）中 HO-1 基因表达增加。体外 HO-1 mRNA 表达增加与 HO-1 蛋白增加相关，这是由于基因转录增加而不是 mRNA 稳定性增加所致。我们表明，高氧对 HO-1 基因的转录激活需要 HO-1 启动子和位于其转录位点上游 4 kb 的增强子片段之间的合作。 HO-1 基因转录的增加与激活蛋白 1 (AP-1) 结合活性的增加以及高氧后 c-Fos 和 c-Jun 抗体对 AP-1 复合物的超移有关。综上所述，我们的数据表明 AP-1 激活可能代表介导高氧诱导 HO-1 基因转录的一种机制。
Using hyperoxia as a model of oxidant-induced lung injury in the rat, we explored the regulation of heme oxygenase-1 (HO-1) expression in vivo and in vitro. We demonstrate marked increase of HO-1 messenger ribonucleic acid (mRNA) levels in rat lungs after hyperoxia. Increased HO-1 mRNA expression correlated with increased HO-1 protein and enzyme activity. Immunohistochemical studies of the rat lung after hyperoxia showed increased HO-1 expression in a variety of cell types, including the bronchoalveolar epithelium and interstitial and inflammatory cells. We then examined the regulation of HO-1 expression in vitro after hyperoxia and observed increased HO-1 gene expression in various cultured cells including epithelial cells, fibroblasts, macrophages, and smooth muscle cells. Increased HO-1 mRNA expression correlated with increased HO-1 protein in vitro, and resulted from increased gene transcription and not from increased mRNA stability. We show that transcriptional activation of the HO-1 gene by hyperoxia requires cooperation between the HO-1 promoter and an enhancer fragment located 4 kb upstream from its transcription site. Increased HO-1 gene transcription was associated with increased activator protein-1 (AP-1) binding activity and supershift of the AP-1 complex by antibodies to c-Fos and c-Jun after hyperoxia. Taken together, our data suggest that AP-1 activation may represent one mechanism mediating hyperoxia-induced HO-1 gene transcription.