Role of innate immune response in liver regeneration
Role of innate immune response in liver regeneration
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DOI：
10.1111/j.1440-1746.2006.04651.x
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发表时间：
2007-06-01
影响因子：
4.1
通讯作者：
Fujimoto, Jiro
中科院分区：
文献类型：
--
作者：
Iimuro, Yuji;Seki, Ekihiro;Fujimoto, Jiro
部分肝切除术（PH）后的肝再生需要几个步骤，包括先天免疫应答，特别是枯否细胞产生的白细胞介素-6（IL-6）和肿瘤坏死因子-（TNF-）α，尽管激活过程仍然未知。Toll样受体（TLR）作为先天性免疫信号传感器，在宿主防御中发挥重要作用。髓样分化因子（MyD）88是TLR介导的信号传导所需的常见接头分子。当受体被激活时，携带TLR的细胞以MyD 88依赖性方式产生各种促炎细胞因子。作者研究了TLR/MyD 88信号传导是否对PH后诱导先天免疫应答至关重要。在PH后的Myd 88（-/-）小鼠中，诱导参与肝细胞复制的立即早期基因的表达以及肝脏中信号转导和转录激活因子3（STAT 3）的磷酸化，Kupffer细胞中TNF-α/IL-6的产生和NF-κ B的活化严重低于正常水平，并与受损的肝再生有关，而识别革兰氏阴性和阳性细菌产物的TLR 2、4和9，结论：TLR/MyD 88通路对PH后肝脏的恢复，特别是早期肝脏的恢复是必不可少的。
Liver regeneration following partial hepatectomy (PH) requires several steps including innate immune responses, particularly interleukin-6 (IL-6) and tumor necrosis factor-(TNF-)alpha production by Kupffer cells, although the activation processes are still unknown. Toll-like receptors (TLR) act as innate immune signal sensors and play central roles in host defense. Myeloid differentiation factor (MyD) 88 is a common adaptor molecule required for signaling mediated by TLR. When the receptors are activated, cells bearing TLR produce various pro-nflammatory cytokines in a MyD88-dependent manner. The authors investigated whether TLR/MyD88 signaling is critical for induction of innate immune responses after PH. In Myd88(-/-) mice after PH, induction of expression of immediate early genes involved in hepatocyte replication and phosphorylation of signal transducer and activators of transcription 3 (STAT3) in the liver, and production of TNF-alpha/IL-6 by and activation of NF-kappa B in the Kupffer cells were grossly subnormal and were associated with impaired liver regeneration, while TLR2, 4 and 9, which recognize Gram-negative and -positive bacterial products, are not essential for NF-kappa B activation and IL-6 production after PH. In conclusion, the TLR/MyD88 pathway is essential for liver restoration after PH, particularly its early phase.