1 Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key laboratory of Organ Transplantation, Ministry of Education, Key laboratory of Organ Transplantation, Ministry of Health, Wuhan, China.2 Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Transplantation. 2017 Jul;101(7):1600-1608. doi: 10.1097/TP.0000000000001765.
MicroRNA-155 (miR-155) is known to be involved in autoimmune diseases, inflammation, and transplantation. However, its role in a warm hepatic ischemia-reperfusion (IR) model has not been fully elucidated.
Partial hepatic IR was performed in wild-type and miR-155-deficient mice treated with or without GdCl3, and then the serum transaminase concentration and histology were analyzed. Kupffer cells (KCs) were isolated from the liver after IR, and immunohistochemistry was used to evaluate activation and polarization. In addition, the mRNA concentrations of various inflammatory cytokines were measured. Macrophages were obtained from the abdominal cavity and challenged with or without lipopolysaccharide to determine the influence of miR-155 deficiency on macrophage polarization in vitro. Furthermore, we used in vitro coculture assays to determine the effect of miR-155 deficiency on hepatocyte apoptosis induced directly by KCs.
miR-155 deficiency ameliorated liver IR injury, and inhibition of KCs by GdCl3 abolished this protective effect. miR-155 deficiency decreased CD80, CD86, and major histocompatibility complex class II expression in KCs after IR and tipped the M1/M2 balance toward an anti-inflammatory profile, where proinflammatory cytokine secretion was suppressed and IL-10 was enhanced. In addition, hepatocyte apoptosis was reduced in coculture with miR-155-deficient KCs in vitro.
miR-155 deficiency plays an effective role in attenuating liver IR injury likely by regulating the activation and inflammatory response, as well as modifying the polarization of KCs.
miR-155（miR-155）已知参与自身免疫性疾病、炎症和移植。然而，其在温热肝缺血再灌注（IR）模型中的作用尚未完全阐明。
对野生型和 miR-155 缺陷型小鼠进行部分肝 IR，并在给予或不给予 GdCl3 的情况下分析血清转氨酶浓度和组织学变化。IR 后从肝脏中分离出枯否细胞（KCs），并用免疫组织化学评估其激活和极化情况。此外，还测量了各种炎症细胞因子的 mRNA 浓度。从腹腔中获得巨噬细胞，并在有无脂多糖的情况下进行刺激，以确定 miR-155 缺陷对体外巨噬细胞极化的影响。此外，我们使用体外共培养实验来确定 miR-155 缺陷对由 KCs 直接诱导的肝细胞凋亡的影响。
miR-155 缺陷可改善肝 IR 损伤，而 GdCl3 抑制 KCs 则消除了这种保护作用。miR-155 缺陷可降低 IR 后 KCs 中 CD80、CD86 和主要组织相容性复合体 II 表达，并使 M1/M2 平衡向抗炎表型倾斜，从而抑制促炎细胞因子的分泌和增强 IL-10。此外，体外共培养中 miR-155 缺陷型 KCs 可减少肝细胞凋亡。
miR-155 缺陷通过调节 KCs 的激活和炎症反应以及改变其极化，在减轻肝 IR 损伤方面发挥有效作用。
