Early release of macrophage migration inhibitory factor after liver ischemia and reperfusion injury in rats
Early release of macrophage migration inhibitory factor after liver ischemia and reperfusion injury in rats
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DOI：
10.1016/j.cyto.2011.11.009
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发表时间：
2012-01-01
期刊：
影响因子：
3.8
通讯作者：
Dahmen, Uta
中科院分区：
文献类型：
--
作者：
Liu, Anding;Fang, Haoshu;Dahmen, Uta
巨噬细胞移动抑制因子（macrophagemigrationinhibitoryfactor，MIF）是心、脑、肠缺血再灌注损伤的重要介质。我们以前证明了MIF在体外热/冷缺血期间释放。然而，MIF在肝I/R损伤中的作用仍不清楚。本研究旨在验证MIF作为一种早期促炎细胞因子介导肝脏I/R炎症损伤的假说。大鼠（n = 6/组）分别行90 min热缺血再灌注0.5 h、6 h和24 h，冷缺血6 h再灌注24 h后行肝移植（LTx）。分析MIF、其受体（分化簇74（CD 74））和下游炎性细胞因子（肿瘤坏死因子-α（TNF-α）和白细胞介素-1 β（IL-1 β））的表达。腹膜巨噬细胞单独培养6小时，或在冷保存肝脏流出物或流出物耗尽MIF的存在下培养6小时。热I/R增加肝脏MIF-mRNA和蛋白表达。MIF-蛋白在体内被释放到外周循环中，在再灌注后0.5小时达到最大值。在这两种模型中，MIF表达的诱导与促炎细胞因子及其受体的表达相关。通过离体冷保存的肝脏释放的MIF诱导培养的腹腔巨噬细胞产生TNF-α和IL-1 β。MIF在肝内的上调，释放到体循环和相关的促炎介质的上调表明MIF在介导I/R损伤的炎症反应中的作用。阻断实验将有助于阐明其作为预防肝I/R损伤的潜在分子靶点的作用。(C)2011爱思唯尔有限公司保留所有权利。
Macrophage migration inhibitory factor (MIF) is an important mediator of ischemia/reperfusion (I/R) injury in heart, brain and intestine. We previously demonstrated that MIF was released during warm/cold ischemia in vitro. However, the role of MIF in liver I/R injury remains unclear. We aimed to test the hypothesis that MIF acts as an early proinflammatory cytokine and could mediate the inflammatory injury in liver I/R. Rats (n = 6 per group) were subjected to 90 min warm ischemia followed by 0.5 h, 6 h and 24 h reperfusion, respectively to liver transplantation (LTx) after 6 h of cold ischemia followed by 24 h of reperfusion. The expression of MIF, its receptor (cluster of differentiation 74 (CD74)) and the downstream inflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta)) were analyzed. Peritoneal macrophages were cultured for 6 h alone or in the presence of effluent from cold-preserved livers or effluent depleted of MIF. Warm I/R increased hepatic MIF-mRNA and protein expression. MIF-protein was released into peripheral circulation in vivo with a maximum at 0.5 h after reperfusion. Induction of MIF-expression was associated with the expression of proinflammatory cytokines and its receptor in both models. MIF released by isolated cold preserved livers, induced TNF-alpha and IL-1 beta production by cultured peritoneal macrophages. Intrahepatic upregulation of MIF, release into systemic circulation and the associated upregulation of the proinflammatory mediators suggest a role of MIF in mediating the inflammatory response to I/R injury. Blocking experiments will help to elucidate its role as potential molecular target for preventing hepatic I/R injury. (C) 2011 Elsevier Ltd. All rights reserved.