Mechanisms of transcriptional activation of lipopolysaccharide binding protein (LBP).
Mechanisms of transcriptional activation of lipopolysaccharide binding protein (LBP).
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发表时间：
1995
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通讯作者：
R. Schumann
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作者：
R. Schumann
脂多糖结合蛋白 (LBP) 对于免疫细胞中内毒素的识别、呈递和随后的细胞因子诱导非常重要。 LBP 是一个不断增长的结构和功能相关蛋白质家族的成员，在肝细胞中合成并组成型分泌到血流中。然而，在急性期反应期间，LBP 水平大幅升高，本文回顾了诱导 LBP 蛋白合成的机制。正如我们通过核连续和 RNA 半衰期实验所证明的那样，肝细胞中 LBP 的诱导是由于转录和转录后机制所致。 LBP 基因 5' 侧翼区域的克隆进一步揭示了典型的急性期蛋白启动子。采用荧光素酶基因和 LBP 启动子突变变体的报告基因测定表明，名为 APRE/STAT-3 的常见急性期启动子基序的完整性对于 LBP 启动子的激活至关重要。转录激活机制的阐明可以为治疗性降低高危患者的 LBP 水平以降低其对革兰氏阴性败血性休克的易感性指明道路。
The Lipopolysaccharide Binding Protein (LBP) is of high importance for endotoxin recognition, presentation and subsequent cytokine induction in immune cells. LBP, which is a member of a growing family of structurally and functionally related proteins, is synthesized in hepatocytes and secreted into the blood stream constitutively. During the acute phase response, however, LBP levels rise substantially and here the mechanisms of induction of LBP protein synthesis were reviewed. The induction of LBP in hepatocytes is due to transcriptional and posttranscriptional mechanisms as we have shown by nuclear run-on and RNA half-life experiments. Cloning of the 5'-flanking region of the LBP gene, furthermore revealed a typical acute phase protein promoter. Reporter gene assays employing the luciferase gene and mutation variants of the LBP promoter revealed that integrity of a common acute phase promoter motif, named APRE/STAT-3 is essential for activation of the LBP promoter. Elucidation of the transcriptional activation mechanism could point the way to a therapeutically lowering of LBP levels in high risk patients for reducing their susceptibility to Gram-negative septic shock.