Peroxisome proliferator activated receptor-γ modulates reactive oxygen species generation and activation of nuclear factor-κB and hypoxia-inducible factor 1α in allergic airway disease of mice
Peroxisome proliferator activated receptor-γ modulates reactive oxygen species generation and activation of nuclear factor-κB and hypoxia-inducible factor 1α in allergic airway disease of mice
复制标题
DOI：
10.1016/j.jaci.2006.03.021
复制
发表时间：
2006-07-01
影响因子：
14.2
通讯作者：
Lee, Yong Chul
中科院分区：
文献类型：
--
作者：
Lee, Kyung Sun;Kim, So Ri;Lee, Yong Chul
背景：活性氧在气道炎症的发病机制中起重要作用。过氧化物酶体增殖物激活受体（PPAR）-γ也参与气道炎症。我们已经证明，给予PPAR γ激动剂或携带PPAR γ cDNA的腺病毒（AdPPAR γ）可减少支气管炎症和气道高反应性。然而，在与气道炎症相关的条件下，过氧化物酶体增殖物激活受体γ对活性氧产生的影响尚未阐明。目的：本研究旨在研究过氧化物酶体增殖物激活受体γ对小鼠过敏性气道疾病中活性氧产生的影响。方法：我们使用雌性C57 BL/6小鼠过敏性气道疾病模型来确定过氧化物酶体增殖物激活受体γ的作用。结果：在这项研究中，用卵清蛋白诱导的过敏性气道疾病小鼠模型，增加的ROS产生和T（H）2细胞细胞因子，粘附分子，趋化因子，和血管内皮生长因子在卵清蛋白吸入后的肺中的显著降低通过施用PPAR γ激动剂或AdPPAR γ。我们还发现，通过给予PPAR γ激动剂或AdPPAR γ，卵白蛋白吸入后肺组织核蛋白提取物中增加的核因子-κ B和缺氧诱导因子let水平降低。这些结果表明，PPAR γ的作用是通过调节ROS的产生和氧化还原敏感性转录因子核因子-κ B和HIF-1 α的活化介导的。临床意义：因此，这些发现提供了一个关键的分子机制，使用过氧化物酶体增殖物激活受体γ激动剂，以预防和/或治疗哮喘和其他气道炎症性疾病。
Background: Reactive oxygen species (ROSs) play a crucial role in the pathogenesis of airway inflammation. Peroxisome proliferator activated receptor (PPAR)-gamma is also involved in airway inflammation. We have demonstrated that the administration of PPAR gamma agonists or adenovirus carrying PPAR gamma cDNA (AdPPAR gamma) reduced bronchial inflammation and airway hyperresponsiveness. However, the effects of PPAR gamma on ROS generation in conditions associated with airway inflammation have not been clarified.Objective: This study aimed to investigate the effects of the PPAR gamma on ROS generation in allergic airway disease of mice.Methods: We have used a female C57BL/6 mouse model for allergic airway disease to determine the role of PPAR gamma.Results: In this study with an ovalbumin-induced murine model of allergic airway disease, the increased ROS generation and the increased expression of T(H)2 cell cytokines, adhesion molecules, chemokines, and vascular endothelial growth factor in lungs after ovalbumin inhalation were significantly reduced by the administration of PPAR gamma agonists or AdPPAR gamma. We also showed that the increased nuclear factor-kappa B and hypoxia-inducible factor let levels in nuclear protein extracts of lung tissues after ovalbumin inhalation were decreased by the administration of PPAR gamma agonists or AdPPAR gamma.Conclusion: These results indicate that the effects of PPAR gamma ire mediated by the modulation of ROS generation and activation of redox-sensitive transcription factor nuclear factor-kappa B and HIF-1 alpha in allergic airway disease of mice.Clinical implications: Thus, these findings provide a pivotal molecular mechanism for the use of PPAR gamma agonists to prevent and/or treat asthma and other airway inflammatory disorders.