Expression of suppressors of cytokine signaling during liver regeneration
Expression of suppressors of cytokine signaling during liver regeneration
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DOI：
10.1172/jci11867
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发表时间：
2001-05-01
影响因子：
15.9
通讯作者：
Fausto, N
中科院分区：
文献类型：
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作者：
Campbell, JS;Prichard, L;Fausto, N
细胞因子TNF和IL-6在部分肝切除术（PH）后的肝再生早期起关键作用。由于IL-6激活信号转导和转录激活因子（STAT），我们研究了细胞因子信号转导抑制因子（SOCS）是否参与终止LL-G信号转导。我们发现SOCS-3 mRNA在手术后2小时被诱导了40倍。SOCS-2和CIS mRNA仅被弱诱导，并且SOCS-1不可检测。PH后SOCS-3诱导是短暂的，与STAT-3 DNA结合减少和酪氨酸705磷酸化丧失相关。这种反应在IL-6敲除（KO）小鼠中显著降低。TNF注射在野生型小鼠中诱导SOCS-3 mRNA（尽管与PH后观察到的增加相比较弱），但在TNF受体1或IL-6 KO小鼠中不诱导。相比之下，IL-6注射在这些动物中诱导SOCS-3，证明在SOCS-3诱导中需要IL-6。除SOCS-3外，向野生型小鼠注射IL-6还诱导SOCS-1、-2和CIS mRNA。总之，这些结果表明SOCS-3可能是PH后下调STAT-3信号传导的关键组分，并且再生肝脏中的SOCS-3 mRNA水平受IL-6调节。
The cytokines TNF and IL-6 play a critical role early in liver regeneration following partial hepatectomy (PH). Since IL-6 activates signal transducers and activators of transcription (STATs), we examined whether the suppressors of cyokine signaling (SOCS) maybe involved in terminating LL-G signaling. We show here that SOCS-3 mRNA is induced 40-fold 2 hours after surgery. SOCS-2 and CIS mRNA are only weakly induced, and SOCS-1 is not detectable. SOCS-3 induction after PH is transient and correlates with a decrease in STAT-3 DNA binding and a loss of tyrosine 705 phosphorylation. This response is markedly reduced in IL-6 knockout (KO) mice. TNF injection induces SOCS-3 mRNA in wild-type mice (albeit weakly compared with the increase observed after PH) but not in TNF receptor 1 or IL-6 KO mice. In contrast, IL-6 injection induces SOCS-3 in these animals, demonstrating a requirement for IL-6 in SOCS-3 induction. IL-6 injection into wild-type mice also induces SOCS-1, -2, and CIS mRNA, in addition to SOCS-3. Together, these results suggest that SOCS-3 may be a key component in downregulating STAT-3 signaling after PH and that SOCS-3 mRNA levels in the regenerating Liver are regulated by IL-6.