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首页> 外文期刊>American Journal of Physiology >Interactions between CBP, NF-kappaB, and CREB in the lungs after hemorrhage and endotoxemia.
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Interactions between CBP, NF-kappaB, and CREB in the lungs after hemorrhage and endotoxemia.

机译：出血和内毒素血症后肺中CBP，NF-κB和CREB之间的相互作用。

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摘要

The transcriptional regulatory factor nuclear factor (NF)-kappaB has a central role in modulating expression of proinflammatory mediators that are important in acute lung injury. In vitro studies have shown that competition between NF-kappaB and cAMP response element binding protein (CREB) for binding to the coactivator CREB-binding protein (CBP) is important in regulating transcriptional activity of these factors. In the present study, we examined in vivo interactions between CBP, CREB, and NF-kappaB in hemorrhage- or endotoxemia-induced acute lung injury. Association of CBP with CREB or the p65 subunit of NF-kappaB increased in the lungs after hemorrhage or endotoxemia. Inhibition of xanthine oxidase before hemorrhage, but not before endotoxemia, decreased p65-CBP interactions while increasing those between CREB and CBP. These alterations in CREB-CBP and p65-CBP interactions were functionally significant because xanthine oxidase inhibition before hemorrhage resulted in increased expression of the CREB-dependent gene c-Fos and decreased expression of macrophage inflammatory protein-2, a NF-kappaB-dependent gene. The present results show that the coactivator CBP has an important role in modulating transcription in vivo under clinically relevant pathophysiological conditions.
机译：转录调节因子核因子（NF）-kappaB在调节在急性肺损伤中很重要的促炎性介质的表达中起着核心作用。体外研究表明，NF-κB和cAMP反应元件结合蛋白（CREB）之间的竞争与辅活化剂CREB结合蛋白（CBP）的结合在调节这些因子的转录活性中很重要。在本研究中，我们检查了出血或内毒素血症引起的急性肺损伤中CBP，CREB和NF-κB的体内相互作用。出血或内毒素血症后，肺中CBP与CREB或NF-κB的p65亚基的关联增加。黄嘌呤氧化酶的抑制作用在出血之前但在内毒素血症之前没有，降低了p65-CBP的相互作用，同时增加了CREB和CBP之间的相互作用。 CREB-CBP和p65-CBP相互作用的这些改变在功能上具有重要意义，因为出血前的黄嘌呤氧化酶抑制导致CREB依赖性基因c-Fos的表达增加以及巨噬细胞炎性蛋白2（一种NF-kappaB依赖性基因）的表达降低。 。目前的结果表明，在临床相关的病理生理条件下，共激活因子CBP在调节体内转录方面具有重要作用。

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