Newton R, Adcock I M, Barnes P J
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK.
Biochem Biophys Res Commun. 1996 Jan 17;218(2):518-23. doi: 10.1006/bbrc.1996.0093.
Epithelial cells are actively involved in inflammation and play a role in inflammatory diseases such as asthma. Numerous proinflammatory genes, expressed in the airway epithelium, are regulated by the transcription factor NF-kappa B. We show that the proinflammatory cytokines, IL-1 beta and TNF alpha, as well as a protein kinase C activator cause NF-kappa B activation in A549 epithelial cells. This observation is consistent with a major role for NF-kappa B in inflammation. We also demonstrate that IL-1 beta costimulation with a protein synthesis inhibitor, cycloheximide, or a transcription blocker, actinomycin D, results in superinduction of NF-kappa B but not the transcription factors Oct 1, AP-1, and Sp-1. We speculate that this may be due to lack of de novo synthesis of the NF-kappa B inhibitor, I kappa B alpha, and suggest that this phenomena may help explain the widely observed effect of mRNA superinduction of primary response genes in response to translational blockers.
上皮细胞积极参与炎症反应，并在诸如哮喘等炎症性疾病中发挥作用。气道上皮中表达的众多促炎基因受转录因子核因子-κB（NF-κB）调控。我们发现，促炎细胞因子白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNFα）以及蛋白激酶C激活剂可导致A549上皮细胞中的NF-κB活化。这一观察结果与NF-κB在炎症中起主要作用相一致。我们还证明，IL-1β与蛋白质合成抑制剂放线菌酮或转录阻断剂放线菌素D共同刺激会导致NF-κB的超诱导，但不会导致转录因子Oct 1、激活蛋白-1（AP-1）和特异性蛋白-1（Sp-1）的超诱导。我们推测这可能是由于缺乏NF-κB抑制剂IκBα的从头合成，并表明这种现象可能有助于解释在翻译阻断剂作用下广泛观察到的初级反应基因mRNA超诱导效应。
