Development of artificial liver support system combining with liver cells and Kuppfer cells.

肝细胞与Kuppfer细胞相结合的人工肝支持系统的开发。

• 批准号: 23591984
• 负责人: FUJII Hideki
• 金额: $ 3.33万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591984/
• 关键词: 肝不全; 人工肝補助装置; 肝Kupffer細胞; GCSF; M-CSF; 新生血管; IL-17; 脾臓摘出; Kupffer細胞; ノックアウトマウス; 肝再生; TNF-α; CD4陽性リンパ球; CLP model; IL-17A; HMGB1; 肝温虚血再還流モデル; glycyrrhizin

IL-17A regulates neutrophil-dependent organ injury. The purpose of this study was to determine the role of IL-17A in neutrophil recruitment after ischemia-reperfusion (I/R). Wild-type (WT) and IL-17A knockout (KO) mice were evaluated. In another experiments, recombinant (rm) IL-17A or rmIL-17A/F were administered before I/R. Isolated Kupffer cells were incubated with rmIL-17A and production of TNF-alpha was measured. The extent of liver injury demonstrated similar levels in the acute phase (6 h) in these two models. In contrast, in the subacute phase (20 h), liver injury were significantly reduced in the KO compared with the WT. This reduction in liver injury was associated with suppression of chemokine, adhesion molecule expression and reduction in infiltration of neutrophils into the liver. TNF-alpha production by isolated Kupffer cells increased significantly with rmIL-17A. IL-17A is a key regulator in initiating neutrophil-induced inflammatory responses and hepatic injury.

IL-17A调节中性粒细胞依赖性器官损伤。这项研究的目的是确定IL-17a在局部缺血再灌注后（I/R）在中性粒细胞募集中的作用。评估了野生型（WT）和IL-17A敲除（KO）小鼠。在另一个实验中，在I/R之前对重组（RM）IL-17A或RMIL-17A/F进行了施用。将分离的库普弗细胞与RMIL-17A孵育，并测量TNF-Alpha的产生。在这两个模型中，肝损伤的程度在急性期（6小时）表现出相似的水平。相反，与WT相比，在KO中，在亚急性相（20小时）中，肝损伤显着降低。肝损伤的减少与趋化因子，粘附分子表达和中性粒细胞浸润到肝脏的降低有关。 RMIL-17A生产的TNF-Alpha产生显着增加。 IL-17A是引发中性粒细胞诱导的炎症反应和肝损伤的关键调节剂。