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首页> 外文期刊>American Journal of Physiology >Hypothermia prolongs activation of NF-kappaB and augments generation of inflammatory cytokines.
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Hypothermia prolongs activation of NF-kappaB and augments generation of inflammatory cytokines.

机译：体温过低会延长NF-κB的活化并增加炎性细胞因子的产生。

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While moderate hypothermia is protective against ischemic cardiac and brain injury, it is associated with much higher mortality in patients with sepsis. We previously showed that in vitro exposure to moderate hypothermia (32 degrees C) delays the induction and prolongs the duration of TNF-alpha and IL-1beta secretion by lipopolysaccharide (LPS)-stimulated human mononuclear phagocytes. In the present study, we extended these observations by showing that moderate hypothermia exerts effects on TNF-alpha and IL-1beta generation in the human THP-1 monocyte cell line that are similar to those that we previously found in primary cultured monocytes; that hypothermia causes comparable changes in cytokine generation stimulated by zymosan, toxic shock syndrome toxin-1, and LPS; and that hypothermia causes similar changes in TNF-alpha and IL-1beta mRNA accumulation. TNF-alpha mRNA half-life, determined after transcriptional arrest with actinomycin D, was not significantly prolonged by lowering incubation temperature from 37 to 32 degrees C, suggesting that hypothermia modifies TNF-alpha gene transcription. This finding was further supported by reporter gene studies showing a threefold increase in activity of the human TNF-alpha promoter at 32 vs. 37 degrees C. Electrophoretic mobility shift assay revealed that hypothermia prolonged NF-kappaBeta activation, identifying a potential role for this transcription factor in mediating the effects of hypothermia on TNF-alpha and IL-1beta production. Delayed reexpression of the inhibitor IkappaBalpha, shown by Northern blotting and immunoblotting, may account in part for the prolonged NF-kappaBeta activation at 32 degrees C. Augmentation of NF-kappaBeta-dependent gene expression during prolonged exposure to hypothermia may be a common mechanism leading to increased lethality in sepsis, late-onset systemic inflammatory response syndrome after accidental hypothermia, and neuroprotection after ischemia.
机译：中度低温可以预防缺血性心脏和脑损伤，但与败血症患者的死亡率高得多有关。我们以前显示，体外暴露于中度低温（32摄氏度）会延迟诱导，并延长脂多糖（LPS）刺激的人单核吞噬细胞分泌TNF-α和IL-1beta的持续时间。在本研究中，我们通过显示中度低温对人THP-1单核细胞系中的TNF-α和IL-1beta生成产生影响，类似于我们先前在原代培养的单核细胞中发现的那些，进行了扩展。低体温引起由酵母聚糖，中毒性休克综合征毒素-1和LPS刺激的细胞因子产生相当的变化;体温过低会导致TNF-α和IL-1beta mRNA积累发生类似变化。通过将孵育温度从37℃降低到32摄氏度，用放线菌素D转录停滞后确定的TNF-αmRNA半衰期没有显着延长，这表明体温过低会改变TNF-α基因的转录。报告基因研究进一步证实了这一发现，该研究表明，人类TNF-α启动子在32摄氏度和37摄氏度下的活性增加了三倍。介导体温过低对TNF-alpha和IL-1beta产生影响的作用。 Northern印迹法和免疫印迹法显示，抑制剂IkappaBalpha的延迟再表达可能部分解释了在32摄氏度时NF-kappaBeta激活时间延长。长时间暴露于体温过低期间NF-kappaBeta依赖基因表达的增强可能是导致这种情况的常见机制导致败血症的致死率增加，意外体温过低导致的迟发性全身炎症反应综合征以及缺血后的神经保护作用。

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