Interleukin-22: implications for liver ischemia-reperfusion injury.
Interleukin-22: implications for liver ischemia-reperfusion injury.
复制标题
DOI：
10.1097/tp.0b013e3182449136
复制
发表时间：
2012-03-15
期刊：
影响因子：
6.2
通讯作者：
Kupiec-Weglinski JW
中科院分区：
文献类型：
--
作者：
Chestovich PJ;Uchida Y;Chang W;Ajalat M;Lassman C;Sabat R;Busuttil RW;Kupiec-Weglinski JW
缺血/再灌注损伤（IRI）在普通外科和器官移植中很常见，对于肝脏来说，它会引发促炎性先天免疫级联反应和肝坏死，导致早期和晚期器官排斥的发生率增加。 IL-22 是一种源自 T 细胞的诱导型细胞因子，属于 IL-10 超家族的成员，通过 IL-22 受体 (IL-22R1) 作用于靶组织。在 C57Bl/6 野生型 (WT) 和 1 型干扰素受体 (IFNAR) 缺陷 (KO) 小鼠中诱导部分肝脏热缺血 90 分钟，然后再灌注 6-24 小时。 WT小鼠在缺血损伤前30分钟用重组IL-22 (rIL-22)或抗IL-22中和抗体(IL-22 Ab)治疗； PBS 和 IgG 作为各自的对照。 IL-22 在肝脏 IRI 24 小时而非 6 小时检测到。 WT 小鼠再灌注 6 小时后，IL-22R1 的表达增加，但免受 IRI 影响的 IFNAR KO 小鼠则没有增加。用 rIL-22 治疗 WT 小鼠可降低 sAST 水平，改善 IR 损伤的主要组织学特征（Suzuki 评分）并减少白细胞隔离，同时增加 IL-22R1 和促炎细胞因子的表达。 IL-22 Ab 不会明显影响 IRI，但会增加肝脏中 IL-22R1 的转录。 IL-22 蛋白的施用通过 STAT3 激活发挥肝保护作用。这是第一份研究 T 细胞衍生的 IL-22 在热缺血和再灌注引起的肝损伤中的免疫调节的报告。 IL-22 蛋白治疗可能代表一种预防移植受者肝脏 IRI 的新治疗策略。
Ischemia/reperfusion injury (IRI) is common in general surgery and organ transplantation, and in the case of liver it triggers pro-inflammatory innate immune cascade and hepatic necrosis, leading to increased incidence of early and late organ rejection. IL-22, an inducible cytokine of T-cell origin and a member of the IL-10 superfamily, acts on target tissues via IL-22 receptor (IL-22R1). Partial hepatic warm ischemia was induced in C57Bl/6 wild-type (WT) and type-1 IFN receptor (IFNAR)-deficient (KO) mice for 90 min followed by 6-24 h of reperfusion. WT mice were treated at 30 min prior to the ischemia insult with recombinant IL-22 (rIL-22) or anti-IL-22 neutralizing antibody (IL-22 Ab); PBS and IgG served as respective controls. IL-22 was detected at 24 h but not 6 h of liver IRI. The expression of IL-22R1 was increased by 6 h of reperfusion in WT but not IFNAR KO mice that were protected from IRI. Treatment of WT mice with rIL-22 decreased sAST levels, ameliorated cardinal histological features of IR damage (Suzuki’s score) and diminished leukocyte sequestration, along with the expression of IL-22R1 and pro-inflammatory cytokines. IL-22 Ab did not appreciably affect IRI but increased IL-22R1 transcription in the liver. Administration of IL-22 protein exerted hepatoprotection via STAT3 activation. This is the first report investigating immune modulation by T cell-derived IL-22 in liver injury due to warm ischemia and reperfusion. Treatment with IL-22 protein may represent a novel therapeutic strategy to prevent liver IRI in transplant recipients.