Zhou Yan, Ficzycz Andrew, Tikoo Suresh Kumar
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Virol J. 2007 Jun 12;4:60. doi: 10.1186/1743-422X-4-60.
Replication-defective (E1-E3 deleted) adenovirus vector based gene delivery results in the induction of cytokines including IL-8, which may contribute to the development of inflammatory immune responses. Like other adenoviruses, E1 + E3 deleted porcine adenovirus (PAdV) 3 induces the production of IL-8 in infected cells. In contrast, no IL-8 production could be detected in cells infected with wild-type or mutant PAdV-3s containing deletion in E1A + E3 (PAV211) or E1Bsmall + E3 (PAV212). Expression of PAdV-3 E1Blarge inhibited the NF-kappaB dependent transcription of luciferase from IL-8 promoter. Imunofluorescence and electrophoretic mobility shift assays suggested that constitutive expression of PAdV-3 E1Blarge inhibited the nuclear translocation of NF-kappaB and its subsequent binding to DNA. These results suggest that E1Blarge interacts with NF-kappaB to prevent transcription and down regulate proinflammatory cytokine IL-8 production.
基于复制缺陷型（E1 - E3缺失）腺病毒载体的基因递送会导致包括白细胞介素 - 8（IL - 8）在内的细胞因子的诱导，这可能有助于炎症免疫反应的发展。与其他腺病毒一样，E1 + E3缺失的猪腺病毒（PAdV）3在感染细胞中诱导IL - 8的产生。相比之下，在用野生型或在E1A + E3（PAV211）或E1B小 + E3（PAV212）中含有缺失的突变型PAdV - 3感染的细胞中未检测到IL - 8的产生。PAdV - 3 E1B大的表达抑制了来自IL - 8启动子的荧光素酶的NF - κB依赖性转录。免疫荧光和电泳迁移率变动分析表明，PAdV - 3 E1B大的组成型表达抑制了NF - κB的核转位及其随后与DNA的结合。这些结果表明，E1B大与NF - κB相互作用以阻止转录并下调促炎细胞因子IL - 8的产生。
