Oxygen-independent stabilization of hypoxia inducible factor (HIF)-1 during RSV infection.
Oxygen-independent stabilization of hypoxia inducible factor (HIF)-1 during RSV infection.
复制标题
RSV感染期间缺氧诱导因子（HIF）-1的氧无氧稳定。
DOI：
10.1371/journal.pone.0003352
复制
发表时间：
2008-10-07
期刊：
影响因子：
3.7
通讯作者：
Eltzschig, Holger K.
中科院分区：
文献类型：
--
作者：
Haeberle, Helene A.;Duerrstein, Carin;Rosenberger, Peter;Hosakote, Yashoda M.;Kuhlicke, Johannes;Kempf, Volkhard A. J.;Garofalo, Roberto P.;Eltzschig, Holger K.
缺氧诱导因子1（HIF）-1α是一种转录因子，在哺乳动物体内氧平衡中起主要调节作用。此外，最近的研究确定了HIF-1α在炎症或感染过程中作为转录调节因子的作用。基于研究表明呼吸道合胞病毒（RSV）是诱导炎症环境的最有效的生物刺激物之一，我们假设HIF-1α在RSV感染期间作为转录调节因子的作用。我们从对RSV感染的人肺上皮细胞进行HIF-1α染色的免疫组织化学研究中获得了第一个见解。这些研究表明，RSV阳性细胞也对HIF-1α染色，表明RSV感染期间伴随HIF活化。同样，Western印迹分析证实RSV感染后24 h HIF-1α蛋白增加约8倍。相比之下，使用UV处理的RSV消除了HIF-1α活化。此外，RSV感染野生型细胞可诱导HIF-α调控的基因（VEGF、CD 73、FN-1、考克斯-2）表达。相反，在肺上皮中，siRNA介导的HIF-1α抑制后，HIF-1α依赖性基因诱导被消除。RSV感染的上皮细胞或对照细胞上清液中氧分压的测量显示氧含量无差异，表明HIF-1α活化不是由RSV相关缺氧引起的。最后，小鼠RSV肺炎的研究证实了小鼠体内模型中的HIF-α激活。总之，这些研究表明，在体外和体内RSV感染期间，HIF-1α的缺氧非依赖性激活。
Hypoxia-inducible factor 1 (HIF)-1α is a transcription factor that functions as master regulator of mammalian oxygen homeostasis. In addition, recent studies identified a role for HIF-1α as transcriptional regulator during inflammation or infection. Based on studies showing that respiratory syncytial virus (RSV) is among the most potent biological stimuli to induce an inflammatory milieu, we hypothesized a role of HIF-1α as transcriptional regulator during infections with RSV. We gained first insight from immunohistocemical studies of RSV-infected human pulmonary epithelia that were stained for HIF-1α. These studies revealed that RSV-positive cells also stained for HIF-1α, suggesting concomitant HIF-activation during RSV infection. Similarly, Western blot analysis confirmed an approximately 8-fold increase in HIF-1α protein 24 h after RSV infection. In contrast, HIF-1α activation was abolished utilizing UV-treated RSV. Moreover, HIF-α-regulated genes (VEGF, CD73, FN-1, COX-2) were induced with RSV infection of wild-type cells. In contrast, HIF-1α dependent gene induction was abolished in pulmonary epithelia following siRNA mediated repression of HIF-1α. Measurements of the partial pressure of oxygen in the supernatants of RSV infected epithelia or controls revealed no differences in oxygen content, suggesting that HIF-1α activation is not caused by RSV associated hypoxia. Finally, studies of RSV pneumonitis in mice confirmed HIF-α-activation in a murine in vivo model. Taking together, these studies suggest hypoxia-independent activation of HIF-1α during infection with RSV in vitro and in vivo.
登录
查看更多内容
影响因子：
29.4
作者：
Cummins, Eoin P.;Seeballuck, Fergal;Taylor, Cormac T.
通讯作者：
Taylor, Cormac T.
影响因子：
20.3
作者：
Eltzschig, HK;Thompson, LF;Colgan, SP
通讯作者：
Colgan, SP
影响因子：
6.7
作者：
Haeberle, HA;Nohé, B;Dieterich, HJ
通讯作者：
Dieterich, HJ
影响因子：
6.4
作者：
Haeberle, HA;Takizawa, R;Garofalo, RP
通讯作者：
Garofalo, RP
DOI：
10.1165/ajrcmb.23.5.f204
发表时间：
2000-11-01
影响因子：
6.4
作者：
Garofalo, RP;Haeberle, H
通讯作者：
Haeberle, H