Interleukin-6 plays a crucial role in the hepatic expression of SOCS3 during acute inflammatory processes in vivo
Interleukin-6 plays a crucial role in the hepatic expression of SOCS3 during acute inflammatory processes in vivo
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DOI：
10.1016/j.jhep.2005.02.048
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发表时间：
2005-10-01
影响因子：
25.7
通讯作者：
Siewert, E
中科院分区：
文献类型：
--
作者：
Yang, XP;Schaper, F;Siewert, E
背景/目标：白细胞介素-6对于损伤后的肝再生和炎症期间急性时相蛋白和细胞色素P450酶的肝表达是必需的。由于其对维持体内平衡的重要贡献，IL-6信号传导受到严格控制。细胞因子信号转导抑制因子（SOCS）3是一种有效的IL-6诱导的反馈抑制剂，可终止IL-6信号转导。然而，几个信号通路汇聚在SOCS 3上：SOCS 3可以在体外被其他介质诱导，并且它并不完全抑制IL-6信号传导。每个细胞因子的诱导SOCS 3在vivo中的个别贡献是unknown.Methods：使用IL-6缺陷小鼠，我们分析了白细胞介素-6的作用，肝SOCS 3的表达响应turtenum和LPS作为模型的无菌和细菌inflammations.Results. In野生型动物，turtenum和LPS引起强烈的诱导SOCS 3。相比之下，IL-6缺陷型小鼠对两种刺激的SOCS 3表达均严重受损：姜黄素未能诱导SOCS 3 mRNA;在LPS诱导的炎症中，LPS注射后60 min的早期诱导反应不存在，SOCS 3的延迟表达显著减少。在IL-6/TNFR-1 knockout mice.Conclusions：我们的数据强烈地认为，在体内急性炎症过程中，IL-6在SOCS 3的肝脏表达中起着至关重要的作用。虽然其他细胞因子能够诱导SOCS 3，但它们的作用似乎很小。(c)2005年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Interleukin-6 is mandatory for liver regeneration after injury and for the hepatic expression of acute phase proteins and cytochrome P450 enzymes during inflammation. Due to its crucial contribution to the maintenance of homeostasis IL-6 signaling is tightly controlled. Suppressor of cytokine signaling (SOCS) 3 is a potent IL-6-induced feedback inhibitor terminating IL-6 signal transduction. However, several signaling pathways converge on SOCS3: SOCS3 can be induced by other mediators in vitro, and it does not exclusively inhibit IL-6 signaling. The individual contribution of each cytokine to the induction of SOCS3 in vivo is unknown.Methods: Using IL-6-deficient mice we analyzed the role of interleukin-6 for the hepatic SOCS3 expression in response to turpentine and LPS as models of aseptic and bacterial inflammation, respectively.Results: In wild-type animals, turpentine and LPS elicited strong induction of SOCS3. IL-6-deficient mice, by contrast, showed severely impaired SOCS3 expression in response to both stimuli: turpentine failed to induce SOCS3 mRNA; in LPS-induced inflammation, the early inductive response 60 min after LPS injection was absent, and the delayed expression of SOCS3 was markedly reduced. The residual delayed SOCS3 expression in IL-6-deficient mice was abolished in IL-6/TNFR-1 knockout mice.Conclusions: Our data strongly argue for a crucial role of IL-6 in the hepatic expression of SOCS3 during acute inflammatory processes in vivo. Although other cytokines are capable of inducing SOCS3 their contribution seems to be minor. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.