Adenovirus E1A gene dysregulates ICAM-1 expression in transformed pulmonary epithelial cells.
Adenovirus E1A gene dysregulates ICAM-1 expression in transformed pulmonary epithelial cells.
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腺病毒 E1A 基因失调转化肺上皮细胞中 ICAM-1 的表达。
DOI：
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发表时间：
1997
影响因子：
6.4
通讯作者：
S. Hayashi
中科院分区：
文献类型：
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作者：
Naoto Keicho;W. Elliott;J. Hogg;S. Hayashi
本实验室的前期研究表明，在慢性阻塞性肺疾病（COPD）患者的肺中检测到腺病毒E1 A DNA和蛋白。由于已知腺病毒E1 A基因产物通过与细胞转录因子相互作用来调节许多基因的表达，我们推测E1 A增强了炎症介质的产生并加剧了吸烟者肺部的炎症过程。为了研究这种可能性，我们用携带腺病毒E1 A基因的质粒转染A549人肺上皮细胞，并分离表达E1 A蛋白的稳定转染子。测试这些产生E1 A的克隆的细胞间粘附分子-1（ICAM-1）表达。与亲本细胞或转染对照质粒的细胞相比，ICAM-1表达在IFN-γ刺激后受到抑制，但在LPS刺激的E1 A阳性细胞中显著增加。这种LPS介导的ICAM-1诱导是血清依赖性的，但在E1 A转染子的表面上未检测到LPS受体CD 14。我们的结论是，E1 A蛋白通过炎症刺激调节ICAM-1的诱导，并使肺上皮细胞对LPS敏感，并表明腺病毒E1 A对炎症介质表达的失调可能会放大吸烟者气道中存在的炎症过程，从而产生COPD。
Previous studies from our laboratory demonstrated that adenovirus E1A DNA and proteins are detected in lungs of patients with chronic obstructive pulmonary disease (COPD). Since adenovirus E1A gene products are known to regulate the expression of many genes by interacting with cellular transcription factors, we postulate that E1A enhances the production of inflammatory mediators and exacerbates the inflammatory process in smokers' lungs. To examine this possibility, we transfected A549 human pulmonary epithelial cells with a plasmid carrying the adenoviral E1A gene and isolated stable transfectants expressing E1A proteins. These E1A-producing clones were tested for intercellular adhesion molecule-1 (ICAM-1) expression. As compared with parental cells or cells transfected with control plasmid, ICAM-1 expression was suppressed after IFN-gamma stimulation but markedly increased by LPS stimulation of E1A-positive cells. This LPS-mediated ICAM-1 induction was serum-dependent but the LPS receptor, CD14, was not detected on the surface of the E1A transfectants. We conclude that E1A proteins modulate ICAM-1 induction by inflammatory stimuli and render lung epithelial cells sensitive to LPS, and suggest that dysregulation of inflammatory mediator expression by adenoviral E1A could amplify the inflammatory process present in airways of smokers to produce COPD.