Kilani Muna M, Mohammed Kamal A, Nasreen Najmunnisa, Tepper Robert S, Antony Veena B
Indiana University Medical Center, Indianapolis, USA.
Inflammation. 2004 Oct;28(5):245-51. doi: 10.1007/s10753-004-6047-y.
RSV infection is characterized by airway edema. Stabilization of hypoxia inducible factor-1alpha (HIF-1alpha) is important in both inflammation and edema formation. In this study we evaluated whether RSV induced release of nitric oxide (NO) by bronchial airway epithelial cells leading to the stabilization of HIF-1alpha and subsequent transcription of VEGF(165). Primary human bronchial epithelial cells (HBEpC) were used; cell supernatants were analyzed. Western blot analysis was used for the detection of HIF-1alpha. Bronchial airway epithelial monolayer permeability was assessed using electric cell-substrate impedance sensing (ECIS) in real time. There was increased stabilization of HIF-1alpha in RSV infected cells. Addition of an NO inhibitor blocked RSV mediated HIF-1alpha expression. Antagonism of NO also inhibited VEGF production and HBEpC monolayer permeability. Our results demonstrate that in HBEpC, RSV induced NO causes stabilization of HIF-1alpha in vitro.
呼吸道合胞病毒（RSV）感染的特征是气道水肿。缺氧诱导因子-1α（HIF-1α）的稳定在炎症和水肿形成过程中均很重要。在本研究中，我们评估了RSV是否通过支气管气道上皮细胞诱导一氧化氮（NO）释放，从而导致HIF-1α稳定以及随后血管内皮生长因子（VEGF）（165）的转录。使用原代人支气管上皮细胞（HBEpC）；对细胞上清液进行分析。采用蛋白质免疫印迹分析检测HIF-1α。实时使用细胞-基质阻抗传感（ECIS）评估支气管气道上皮单层通透性。RSV感染的细胞中HIF-1α的稳定性增加。添加NO抑制剂可阻断RSV介导的HIF-1α表达。抑制NO也可抑制VEGF产生和HBEpC单层通透性。我们的结果表明，在HBEpC中，RSV诱导的NO在体外导致HIF-1α稳定。
