IL-4 通过 STAT6-JMJD3 通路诱导肝移植后枯否细胞 M2 极化减轻缺血再灌注损伤。
IL-4 Alleviates Ischaemia-Reperfusion Injury by Inducing Kupffer Cells M2 Polarization via STAT6-JMJD3 Pathway after Rat Liver Transplantation.
机构信息
Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Department of Hepatobiliary Surgery, Suining Central Hospital, Suining, Sichuan 629000, China.
出版信息
Biomed Res Int. 2020 Mar 18;2020:2953068. doi: 10.1155/2020/2953068. eCollection 2020.
BACKGROUND
Liver ischaemia-reperfusion injury (IRI) remains a problem in liver transplantation. Interleukin-4 (IL-4) has been found to reduce liver IRI, but the exact mechanism remains unclear.
METHODS
Donor livers were infused with recombinant IL-4 or normal saline during cold storage, and the hepatocellular apoptosis and the inflammatory response were detected. The effect of IL-4 treatment on Kupffer cells (KCs) polarization and expression of the STAT6-JMJD3 pathway was evaluated and . KCs in donor livers were depleted by clodronate liposome treatment or JMJD3 was inhibited by GSK-J4 before liver transplantation to determine whether the protective effect of IL-4 treatment was dependent on KCs.
RESULTS
IL-4 treatment decreased sALT and sAST levels and alleviated hepatocellular apoptosis and inflammation at 6 h after liver transplantation. IL-4 treatment induced KCs alternatively activated (M2) polarization . KCs in donor livers were depleted by clodronate liposome treatment or JMJD3 was inhibited by GSK-J4 before liver transplantation to determine whether the protective effect of IL-4 treatment was dependent on KCs. and . KCs in donor livers were depleted by clodronate liposome treatment or JMJD3 was inhibited by GSK-J4 before liver transplantation to determine whether the protective effect of IL-4 treatment was dependent on KCs.
CONCLUSIONS
IL-4 treatment-induced KCs M2 polarization was dependent on the STAT6-JMJD3 pathway and protected liver grafts from IRI after liver transplantation.
背景
肝缺血再灌注损伤（IRI）仍是肝移植中的一个问题。已发现白细胞介素 4（IL-4）可减少肝IRI，但确切机制仍不清楚。
方法
在冷保存期间，供体肝脏用重组 IL-4 或生理盐水输注，并检测肝细胞凋亡和炎症反应。评估了 IL-4 处理对库普弗细胞（KCs）极化和 STAT6-JMJD3 途径表达的影响。在肝移植前，用氯膦酸盐脂质体处理或用 GSK-J4 抑制 JMJD3，以耗尽供体肝脏中的 KCs，以确定 IL-4 处理的保护作用是否依赖于 KCs。
结果
IL-4 处理可降低 sALT 和 sAST 水平，并减轻肝移植后 6 小时的肝细胞凋亡和炎症。IL-4 处理诱导 KCs 替代激活（M2）极化。在肝移植前，用氯膦酸盐脂质体处理或用 GSK-J4 抑制 JMJD3，以耗尽供体肝脏中的 KCs，以确定 IL-4 处理的保护作用是否依赖于 KCs。在肝移植前，用氯膦酸盐脂质体处理或用 GSK-J4 抑制 JMJD3，以耗尽供体肝脏中的 KCs，以确定 IL-4 处理的保护作用是否依赖于 KCs。
结论
IL-4 处理诱导的 KCs M2 极化依赖于 STAT6-JMJD3 途径，并可保护肝移植物免受肝移植后的 IRI。
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