Relationship Between HMGB1 and Tissue Protective Effects of HSP72 in a LPS-Induced Systemic Inflammation Model
Relationship Between HMGB1 and Tissue Protective Effects of HSP72 in a LPS-Induced Systemic Inflammation Model
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DOI：
10.1016/j.jss.2009.10.015
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发表时间：
2011-07-01
影响因子：
2.2
通讯作者：
Noguchi, Takayuki
中科院分区：
文献类型：
--
作者：
Hasegawa, Akira;Iwasaka, Hideo;Noguchi, Takayuki
背景。热休克蛋白72（HSP72(a)）在炎症反应中表现出细胞和器官的保护作用。此外，高迁移率组框1 （HMGB1）蛋白是急性炎症的酒精介质。在脂多糖（LPS(b)）诱导的炎症模型中，我们检测了全身热疗（WH）诱导HSP72时观察到的HMGB1表达与保护作用之间的关系。材料与方法。分析肝素治疗后血清细胞因子、HMGB1水平及肺组织HSP72、HMGB1表达情况。在RAW264.7细胞中，我们进一步观察了HSP72的预先诱导和沉默对HMGB1分泌的影响。生存率从LPS组的33%显著提高到WH + LPS组的78%。白介素-6、肿瘤坏死因子-a和HMGB1浓度显著降低。此外，治疗后的大鼠肺部炎症减轻。预先诱导HSP72可显著降低RAW264.7细胞HMGB1的分泌，而沉默HSP72可阻止这种减少。我们的研究结果表明，在lps诱导的全身炎症模型中，热预处理诱导的HSP72可以减少炎症并提高生存率。这些作用与抑制HMGB1表达有关，可能涉及热休克蛋白介导的HMGB1分泌抑制。(C) 2011爱思唯尔公司版权所有。
Background. Heat shock protein 72 (HSP72(a)) exhibits cell-and organ-protective effects in response to inflammation. Moreover, high mobility group box 1 (HMGB1) protein isalethalmediator of acute inflammation. We examined associations between HMGB1 expression and protective effects observed when whole body hyperthermia (WH) induces HSP72 in a lipopolysaccharide (LPS(b))-induced inflammation model.Materials and Methods. Serum cytokine and HMGB1 levels, as well as HSP72 and HMGB1 expression in lung tissue were analyzed after WH treatment. Furthermore, effects of prior induction of HSP72 and silencing of HSP72 on HMGB1 secretion were examined in cultured RAW264.7 cells.Results. Survival improved significantly from 33% in the LPS group to 78% in the WH + LPS group. Interleukin-6, tumor necrosis factor-a, and HMGB1 concentrations were significantly lower in WH-treated rats. Furthermore, inflammation was reduced in lungs of WH-treated rats. Prior induction of HSP72 resulted in significantly decreased HMGB1 secretion by RAW264.7 cells in vitro, while silencing of HSP72 prevented this decrease.Conclusions. Our results suggest that HSP72 induction by thermal pretreatment reduced inflammation and improved survival in the LPS-induced systemic inflammation model. These effects, which were associated with inhibition of HMGB1 expression, potentially involve HSP-mediated inhibition of HMGB1 secretion. (C) 2011 Elsevier Inc. All rights reserved.