In vivo heat shock protein assembles with septic liver NF-κB/I-κB complex regulating NF-κB activity
In vivo heat shock protein assembles with septic liver NF-κB/I-κB complex regulating NF-κB activity
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DOI：
10.1097/01.shk.0000174020.87439.f2
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发表时间：
2005-09-01
期刊：
影响因子：
3.1
通讯作者：
Yang, RC
中科院分区：
文献类型：
--
作者：
Chen, HW;Kuo, HT;Yang, RC
这项研究阐明了热休克治疗影响脓毒症结局的机制。全身热疗24小时后CLP诱导大鼠热休克败血症。收集并分析早期和晚期脓毒症大鼠的肝细胞质和细胞核部分（分别在 CLP 后 9 小时和 18 小时处死）。脓毒症期间，肝细胞质中的 I-kappa B 和核因子 kappa B (NF-kappa B) 水平下降，而细胞核中的 NF-kappa B 水平增加。脓毒症期间NF-κB活性显着增强，并且NF-κB靶基因的产物，如TNF-α和诱导型一氧化氮合酶（NOS）过度表达。热休克处理诱导热休克蛋白合成，防止胞质 I-κ B 的下调，并减少 NF-κ B 进入细胞核的易位。因此，脓毒症引起的 NF-κ B 激活加速受到抑制。 TNF-a 和 NOS mRNA 的表达也下调。抗 NF-kappa B (p65) 和抗 I kappa B 抗体的共免疫沉淀证实了热休克蛋白 (HSP) 72 与 NF-kappa B 和 I-kappa B 的组装现象。我们认为，防止 NF-kappa B 败血症激活的机制是过度合成的 HSP72 与 NF-kappa 形成复合物 B/l-kappa B，从而抑制 NF-kappa B 的核转位。HSP72 似乎在脓毒症中调节 NF-kappa B 控制的基因表达中发挥着至关重要的保护作用。
This study elucidates the mechanism through which heat shock treatment influences the outcome of sepsis. Post-heat shock sepsis was induced in rats by CLP 24 h after whole-body hyperthermia. Liver cytosolic and nuclear fractions were collected and analyzed in early and late sepsis rats (sacrificed 9 and 18 h after CLP, respectively). During sepsis, levels of I-kappa B and nuclear factor-kappa B (NF-kappa B) declined in the cytosol of liver, whereas NF-kappa B increased in nucleus. NF-kappa B activity was significantly enhanced during sepsis, and the products of NF-kappa B target genes, such as TNF-alpha and inducible nitric oxide synthase (NOS), were overexpressed. Heat shock treatment, inducing heat shock protein synthesis, prevented down-regulation Of cytosolic I-kappa B and decreased translocation of NF-kappa B into the nucleus. Therefore, the sepsisinduced acceleration of NF-kappa B activation was inhibited. Expression of TNF-a and NOS mRNA was also down-regulated. Coirnmunoprecipitation with anti-NF-kappa B (p65) and anti-I kappa B antibodies verified an assembling phenomenon of heat shock protein (HSP) 72 with NF-kappa B and I-kappa B. We suggest that the mechanism preventing septic activation of NF-kappa B is that oversynthesized HSP72 forms a complexwith NF-kappa B/l-kappa B, thus inhibiting nuclear translocation of NF-kappa B. HSP72 appears to play a crucial protective role in modulating the gene expression controlled by NF-kappa B in sepsis.