Cutting edge: High-mobility group box 1 preconditioning protects against liver ischemia-reperfusion injury
Cutting edge: High-mobility group box 1 preconditioning protects against liver ischemia-reperfusion injury
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DOI：
10.4049/jimmunol.176.12.7154
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发表时间：
2006-06-15
影响因子：
4.4
通讯作者：
Billiar, Timothy R.
中科院分区：
文献类型：
--
作者：
Izuishi, Kunihiko;Tsung, Allan;Billiar, Timothy R.
高迁移率族蛋白1（HMGB 1）是一种细胞外释放的NF，作为脓毒症中致死性的晚期介质和损伤后炎症的早期介质。在这里，我们证明了与HMGB 1的促炎作用相反，HMGB 1预处理导致肝缺血/再灌注（I/R）后的保护作用。用HMGB 1预处理小鼠可显著减轻I/R后的肝损伤。与对照组相比，在用HMGB 1预处理的小鼠中观察到的保护作用与IL-1 R相关激酶-M的较高表达有关，IL-1 R相关激酶-M是TLR 4信号传导的负调节因子。因此，我们探讨了HMGB 1预处理通过TLR 4激活介导的可能性。HMGB 1预处理未能在TLR 4突变型（C3 H/HeJ）小鼠中提供保护，但成功地减少了TLR 4野生型（C3 H/HeOuj）小鼠中的损伤。我们的研究表明，与HMGB 1在肝脏I/R中作为炎症和器官损伤的早期介质的作用相反，HMGB 1预处理可以具有保护作用。
High mobility group box 1 (HMGB1) is a NF released extracellularly as a late mediator of lethality in sepsis and as an early mediator of inflammation following injury. Here we demonstrate that in contrast to the proinflammatory role of HMGB1, preconditioning with HMGB1 results in protection following hepatic ischemia/reperfusion (I/R). Pretreatment of mice with HMGB1 significantly decreased liver damage after I/R. The protection observed in micepretreated with HMGB1 was associated with a higher expression of IL-IR-associated kinase-M, a negative regulator of TLR4 signaling, compared with controls. We thus explored the possibility that HMGB1 preconditioning was mediated through TLR4 activation. HMGB1 preconditioning failed to provide protection in TLR4 mutant (C3H/HeJ) mice, but successfully reduced damage in TLR4 wild-type (C3H/HeOuj) mice. Our studies demonstrate that in contrast to the role of HMGB1 as an early mediator of inflammation and organ damage in hepatic I/R, HMGB1 preconditioning can be protective.