Induction of heme oxygenase-1, biliverdin reductase and H-ferritin in lung macrophage in smokers with primary spontaneous pneumothorax: role of HIF-1alpha.
Induction of heme oxygenase-1, biliverdin reductase and H-ferritin in lung macrophage in smokers with primary spontaneous pneumothorax: role of HIF-1alpha.
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DOI：
10.1371/journal.pone.0010886
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发表时间：
2010-05-28
期刊：
影响因子：
3.7
通讯作者：
Bonay M
中科院分区：
文献类型：
--
作者：
Goven D;Boutten A;Leçon-Malas V;Marchal-Sommé J;Soler P;Boczkowski J;Bonay M
很少有资料涉及与肺泡缺氧/复氧相关的原发性自发性气胸(PSP)的病理生理学。这项研究验证了PSP与肺巨噬细胞氧化应激有关的假设。我们分析了氧化应激标志物4-HNE、抗氧化和抗炎蛋白血红素加氧酶-1(HO-1)、胆绿素还原酶(BVR)和铁蛋白重链(H-铁蛋白)及其调控转录因子NRF2和HIF-1α在吸烟者和非吸烟者肺组织(PSP-S和PSP-NS)中的表达，发现吸烟是疾病复发的危险因素。RT-PCR法检测mRNA表达，Western印迹、免疫组织化学和激光共聚焦分析检测蛋白质表达。PSP-S组巨噬细胞4-HNE、HO-1、BVR和H-铁蛋白均高于PSP-NS组和对照组(C)。PSP-S患者肺泡巨噬细胞HO-1表达增加与HIF-1NRF2基因和蛋白表达增加相关，而α表达无改变。为了了解HO-1、BVR和H-铁蛋白的调节，将THP-1巨噬细胞暴露在模拟C、PSP-S和PSP-NS患者的条件下：香烟烟雾冷凝物(CS)或暴露于空气中，然后/或不暴露于缺氧/复氧。沉默核糖核酸实验证实，HIF-1α核转位与CS和缺氧/复氧诱导的HO-1、BVR和H-铁蛋白的诱导有关。吸烟者的PSP与肺巨噬细胞氧化应激有关。对这种情况的反应包括HIF-1α介导的HO-1、BVR和H-铁蛋白的诱导。
Few data concern the pathophysiology of primary spontaneous pneumothorax (PSP), which is associated with alveolar hypoxia/reoxygenation. This study tested the hypothesis that PSP is associated with oxidative stress in lung macrophages. We analysed expression of the oxidative stress marker 4-HNE; the antioxidant and anti-inflammatory proteins heme oxygenase-1 (HO-1), biliverdin reductase (BVR) and heavy chain of ferritin (H-ferritin); and the transcription factors controlling their expression Nrf2 and HIF-1α, in lung samples from smoker and nonsmoker patients with PSP (PSP-S and PSP-NS), cigarette smoke being a risk factor of recurrence of the disease. mRNA was assessed by RT-PCR and proteins by western blot, immunohistochemistry and confocal laser analysis. 4-HNE, HO-1, BVR and H-ferritin were increased in macrophages from PSP-S as compared to PSP-NS and controls (C). HO-1 increase was associated with increased expression of HIF-1α mRNA and protein in alveolar macrophages in PSP-S patients, whereas Nrf2 was not modified. To understand the regulation of HO-1, BVR and H-ferritin, THP-1 macrophages were exposed to conditions mimicking conditions in C, PSP-S and PSP-NS patients: cigarette smoke condensate (CS) or air exposure followed or not by hypoxia/reoxygenation. Silencing RNA experiments confirmed that HIF-1α nuclear translocation was responsible for HO-1, BVR and H-ferritin induction mediated by CS and hypoxia/reoxygenation. PSP in smokers is associated with lung macrophage oxidative stress. The response to this condition involves HIF-1α-mediated induction of HO-1, BVR and H-ferritin.
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