Hyperthermia-induced heat shock activates the transcription factor C/EBP-β and augments IL-6 production in human intestinal epithelial cells
Hyperthermia-induced heat shock activates the transcription factor C/EBP-β and augments IL-6 production in human intestinal epithelial cells
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DOI：
10.1016/s1072-7515(02)01342-x
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发表时间：
2002-11-01
影响因子：
5.2
通讯作者：
Hasselgren, PO
中科院分区：
文献类型：
--
作者：
Hungness, ES;Robb, BW;Hasselgren, PO
背景：脓毒症和内毒素血症时肠粘膜产生白细胞介素（IL）-6。在这些条件下，热休克反应增加IL-6的产生，但其机制尚不清楚。我们假设，热休克刺激IL-6的生产在肠上皮细胞的转录因子C/EBP的表达和活性增加。研究设计：培养的Caco-2细胞，人肠上皮细胞系，经历了诱导的热休克反应的高温（43 degreesC为1小时）。其他细胞保持在37 ℃。然后用0.5 ng/mL人重组IL-1 β处理细胞4小时。C/EBP-β和δ DNA结合活性通过电泳迁移率变动分析和超变动分析测定。结果：表达热休克反应的Caco-2细胞中C/EBP-β蛋白水平和DNA结合活性明显升高，而δ蛋白水平和DNA结合活性无明显变化。诱导热休克反应增强IL-1 β处理过的细胞过度表达C/EBP-β的IL-6的生产，但不delta.CONCLUSIONS：IL-1 β处理过的肠上皮细胞表达热休克反应的IL-6的生产增加可能是由于上调C/EBP-β的表达和活性。由于最近的研究表明，IL-6可能是一种细胞因子，并可能发挥保护作用，在肠道粘膜和肠细胞，了解机制，热休克反应增加IL-6的生产可能有重要的临床意义。(C)2002年由美国外科医生学会。
BACKGROUND: Interleukin (IL)-6 production is increased in gut mucosa during sepsis and endotoxemia. The heat shock response augments IL-6 production under these conditions, but the mechanism is not known. We hypothesized that heat shock stimulates IL-6 production in enterocytes by increasing expression and activity of the transcription factor C/EBP.STUDY DESIGN: Cultured Caco-2 cells, a human intestinal epithelial cell line, underwent induction of the heat shock response by hyperthermia (43degreesC for I hour). Other cells were kept at 37degreesC. Cells were then treated with 0.5 ng/mL human recombinant IL-1beta for 4 hours. C/EBP-beta and delta DNA binding activity was determined by electrophoretic mobility shift assay and supershift analysis. In additional experiments, Caco-2 cells were transfected with expression plasmids for C/EBP-beta and delta, after which cells were subjected to hyperthermia and treatment with IL-1beta.RESULTS: C/EBP-beta, but not delta, protein levels and DNA binding activity were increased in Caco-2 cells expressing the heat shock response. Induction of the heat shock response augmented IL-6 production in IL-1beta-treated cells overexpressing C/EBP-beta, but not delta.CONCLUSIONS: Increased IL-6 production in IL-1beta-treated enterocytes expressing the heat shock response might be caused by upregulated expression and activity of C/EBP-beta. Because recent studies suggest that IL-6 might be an antiinflammatory cytokine and might exert protective effects in gut mucosa and enterocytes, understanding mechanisms by which the heat shock response augments IL-6 production might have important clinical implications. (C) 2002 by the American College of Surgeons.