Oxidant stress responses in influenza virus pneumonia: Gene expression and transcription factor activation
Oxidant stress responses in influenza virus pneumonia: Gene expression and transcription factor activation
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DOI：
10.1152/ajplung.1996.271.3.l383
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发表时间：
1996-09-01
影响因子：
4.9
通讯作者：
Jacoby, DB
中科院分区：
文献类型：
--
作者：
Choi, AMK;Knobil, K;Jacoby, DB
流感病毒感染肺部的发病机制部分是由氧化应激介导的。因此，这种感染可能会诱导应激反应基因和编码抗氧化酶的基因的表达，并激活转录调节蛋白。用流感病毒A/PR/8/34（H1N1）鼻内感染小鼠（C57 B1/6和C3 H/HeJ）。编码抗氧化酶锰超氧化物歧化酶（MnSOD），吲哚胺-2，3-双加氧酶（IDO），血红素加氧酶-1，谷胱甘肽过氧化物酶的基因的表达在病毒感染动物的肺中增加。Cu/ZnSOD和过氧化氢酶mRNA不受病毒感染的诱导。病毒感染后，通过电泳迁移率变动试验证明了转录调节蛋白AP-1、C/EBP和NF-κ B（已知受氧化应激影响）的激活。在MnSOD的情况下，尽管基因表达增加，酶活性没有增加。相反，血红素氧合酶-1的mRNA和活性都增加。已知C3 H/HeJ和C57 B1/6小鼠对其他类型的氧化应激具有不同的反应，它们对病毒感染的反应也不同。血红素氧合酶-1的表达诱导C57 B1/6小鼠比C3 H/HeJ小鼠，虽然抑制这种酶并没有改变病毒诱导的死亡率。相反，IDO在C3 H/HeJ小鼠中被更强烈地诱导。NF-κ B的活化在C57 B1/6小鼠中比在C3 H/HeJ小鼠中显著得多。虽然病毒复制和炎症反应是等效的两种菌株，肺损伤（湿干重比测量）和死亡率是更大的C3 H/HeJ小鼠比C57 B1/6小鼠，差异可能与不同的氧化应激反应。因此，流感性肺炎会在肺部引起氧化应激反应，其性质部分取决于宿主的遗传背景。
The pathogenesis of influenza virus infections of the lungs is in part mediated by oxidative stress. Such infections might therefore be expected to induce expression of stress-response genes and genes encoding antioxidant enzymes and to activate transcriptional regulatory proteins. Mice (C57B1/6 and C3H/HeJ) were infected intranasally with influenza virus A/PR/8/34 (H1N1). Expression of the genes encoding the antioxidant enzymes manganese superoxide dismutase (MnSOD), indoleamine-2,3-dioxygenase (IDO), heme oxygenase-1, and glutathione peroxidase were increased in the lungs of virus-infected animals. Cu/ZnSOD and catalase mRNA were not induced by viral infection. Activation of the transcriptional regulatory proteins AP-1, C/EBP, and NF-kappa B (which are known to be affected by oxidant stress) was demonstrated by electrophoretic mobility shift assay after viral infection. In the case of MnSOD, despite increased gene expression enzyme activity was not increased. In contrast, for heme oxygenase-1 both mRNA and activity were increased. C3H/HeJ and C57B1/6 mice, which are known to have different responses to other types of oxidant stress, also differed in their responses to viral infection. Induction of heme oxygenase-1 expression was greater in C57B1/6 mice than in C3H/HeJ mice, although inhibiting this enzyme did not alter virus-induced mortality. In contrast, IDO was more strongly induced in C3H/HeJ mice. Activation of NF-kappa B was much more marked in C57B1/6 mice than in C3H/HeJ mice. Although virus replication and inflammatory responses were equivalent in the two strains, lung injury (as measured by wet-to-dry wt ratios) and mortality were greater in C3H/HeJ mice than in C57B1/6 mice, a difference that may be related to differing oxidant stress responses. Thus influenza pneumonia causes an oxidant stress response in the lungs, the nature of which is determined in part by the genetic background of the host.