Keicho N, Higashimoto Y, Bondy G P, Elliott W M, Hogg J C, Hayashi S
Third Department of Internal Medicine, University of Tokyo, Tokyo 113, Japan.
Am J Physiol. 1999 Sep;277(3):L523-32. doi: 10.1152/ajplung.1999.277.3.L523.
Adenovirus E1A DNA and proteins are detected in lung epithelial cells of patients with chronic obstructive pulmonary disease. In investigating E1A regulation of inflammatory mediator expression in human lung epithelial cells, we found increased intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 expression after lipopolysaccharide (LPS) stimulation of A549 cells stably transfected with adenovirus 5 E1A. We now show that E1A-dependent induction of interleukin-8 expression is specific to LPS, superinduced by cycloheximide, and not observed after tumor necrosis factor or phorbol 12-myristate 13-acetate stimulation. Electrophoretic mobility shift assays revealed that tumor necrosis factor or phorbol 12-myristate 13-acetate induced nuclear factor-kappaB binding complexes of Rel A and p50 in E1A and control transfectants, whereas LPS was effective only in E1A transfectants. Similarly, LPS-induced nuclear translocation of nuclear factor-kappaB was observed only in E1A transfectants. CCAAT-enhancer binding protein binding was undetected and activator protein-1 binding was unaffected by LPS in either cell type, whereas basal mRNA levels of c-jun were unchanged by E1A. We conclude that E1A enhances the expression of these inflammatory mediator genes by modulating events specific to LPS-triggered nuclear factor-kappaB induction in these cells.
在慢性阻塞性肺疾病患者的肺上皮细胞中检测到腺病毒E1A DNA和蛋白。在研究E1A对人肺上皮细胞中炎症介质表达的调控时，我们发现用腺病毒5 E1A稳定转染的A549细胞在脂多糖（LPS）刺激后，细胞间黏附分子-1（ICAM-1）和白细胞介素-8的表达增加。我们现在表明，E1A依赖的白细胞介素-8表达诱导对LPS具有特异性，可被放线菌酮超诱导，而在肿瘤坏死因子或佛波酯12-肉豆蔻酸酯13-乙酸酯刺激后未观察到。电泳迁移率变动分析显示，肿瘤坏死因子或佛波酯12-肉豆蔻酸酯13-乙酸酯在E1A和对照转染细胞中诱导Rel A和p50的核因子-κB结合复合物，而LPS仅在E1A转染细胞中有效。同样，仅在E1A转染细胞中观察到LPS诱导的核因子-κB核转位。在两种细胞类型中均未检测到CCAAT增强子结合蛋白结合，LPS对激活蛋白-1结合无影响，而E1A对c-jun的基础mRNA水平无改变。我们得出结论，E1A通过调节这些细胞中LPS触发的核因子-κB诱导的特异性事件来增强这些炎症介质基因的表达。
