Interleukin-1 receptor antagonist modulates the early phase of liver regeneration after partial hepatectomy in mice.
Interleukin-1 receptor antagonist modulates the early phase of liver regeneration after partial hepatectomy in mice.
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DOI：
10.1371/journal.pone.0025442
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Buhler L
中科院分区：
文献类型：
--
作者：
Sgroi A;Gonelle-Gispert C;Morel P;Baertschiger RM;Niclauss N;Mentha G;Majno P;Serre-Beinier V;Buhler L
细胞因子给药通过减少炎症反应和促进肝细胞再生，是急性肝衰竭的潜在治疗方法。本研究旨在探讨白细胞介素1受体拮抗剂（IL-1 ra）在肝再生过程中的作用，并研究重组人IL-1 ra对肝再生的影响。我们在野生型（WT）小鼠、IL-1 ra敲除（KO）小鼠和阿那白滞素治疗的WT小鼠中进行了70%肝切除术。我们定期通过测量细胞因子的血液水平、通过溴脱氧尿苷（BrdU）掺入的肝细胞增殖、增殖细胞核抗原（PCNA）和细胞周期蛋白D1表达来分析肝再生。阿那白滞素对肝细胞增殖的影响也在体外使用人肝细胞进行了测试。在肝切除术后24小时和48小时，与WT小鼠相比，IL-1 ra KO小鼠具有显著更高水平的促炎细胞因子（IL-6、IL-1β和MCP-1），并且通过BrdU掺入、PCNA和Cyclin D1蛋白水平测量的肝细胞增殖减少和延迟。与WT小鼠相比，IL-1 ra KO小鼠IGFBP-1和C/EBPβ表达显著降低。与未处理的WT小鼠相比，用阿那白滞素处理的WT小鼠在24小时显示出显著降低的IL-6水平和显著更高的肝细胞增殖。在体外，与未处理的肝细胞相比，用阿那白滞素处理的原代人肝细胞在24小时显示出显著更高的增殖。IL 1 ra通过降低炎症应激和促进肝细胞进入增殖来调节肝再生的早期阶段。IL 1 ra可能是促进肝细胞增殖的治疗靶点。
Cytokine administration is a potential therapy for acute liver failure by reducing inflammatory responses and favour hepatocyte regeneration. The aim of this study was to evaluate the role of interleukin-1 receptor antagonist (IL-1ra) during liver regeneration and to study the effect of a recombinant human IL-1ra on liver regeneration. We performed 70%-hepatectomy in wild type (WT) mice, IL-1ra knock-out (KO) mice and in WT mice treated by anakinra. We analyzed liver regeneration at regular intervals by measuring the blood levels of cytokines, the hepatocyte proliferation by bromodeoxyuridin (BrdU) incorporation, proliferating cell nuclear antigen (PCNA) and Cyclin D1 expression. The effect of anakinra on hepatocyte proliferation was also tested in vitro using human hepatocytes. At 24h and at 48h after hepatectomy, IL-1ra KO mice had significantly higher levels of pro-inflammatory cytokines (IL-6, IL-1β and MCP-1) and a reduced and delayed hepatocyte proliferation measured by BrdU incorporation, PCNA and Cyclin D1 protein levels, when compared to WT mice. IGFBP-1 and C/EBPβ expression was significantly decreased in IL-1ra KO compared to WT mice. WT mice treated with anakinra showed significantly decreased levels of IL-6 and significantly higher hepatocyte proliferation at 24h compared to untreated WT mice. In vitro, primary human hepatocytes treated with anakinra showed significantly higher proliferation at 24h compared to hepatocytes without treatment. IL1ra modulates the early phase of liver regeneration by decreasing the inflammatory stress and accelerating the entry of hepatocytes in proliferation. IL1ra might be a therapeutic target to improve hepatocyte proliferation.
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影响因子：
13.5
作者：
Cosgrove, Benjamin D.;Cheng, Connie;Pritchard, Justin R.;Stolz, Donna B.;Lauffenburger, Douglas A.;Griffith, Linda G.
通讯作者：
Griffith, Linda G.
影响因子：
13.5
作者：
Jin, XL;Zimmers, TA;Koniaris, LG
通讯作者：
Koniaris, LG
DOI：
10.1073/pnas.93.20.11008
发表时间：
1996-10-01
影响因子：
11.1
作者：
Hirsch, E;Irikura, VM;Hirsh, D
通讯作者：
Hirsh, D
影响因子：
6.2
作者：
Harada, H;Wakabayashi, G;Kitajima, M
通讯作者：
Kitajima, M
影响因子：
5.3
作者：
Leu, JI;Crissey, MAS;Taub, R
通讯作者：
Taub, R