Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
Cell Biol Int. 2019 May;43(5):495-505. doi: 10.1002/cbin.11115. Epub 2019 Mar 12.
Peritoneal dialysis (PD) is often used to treat patients with end stage renal disease, and its long-term complications include excessive inflammation and oxidative stress. Allograft inflammatory factor 1 (AIF-1), as a cytoplasmic protein, is originally identified from infiltrating macrophages, and it was associated with inflammation in the cells other than macrophages, such as endothelial cells and vascular smooth muscle cells. To clarify the molecular mechanisms of AIF-1-modulated pathological changes in the peritoneum during PD, we first detected the AIF-1 expression in peritoneal tissues from PD mice. Results revealed that the pro-fibrotic stimulation caused AIF-1 upregulation and triggered inflammation in peritoneal tissues, and that AIF-1 co-expressed with pan-cytokeratin (a marker of peritoneal mesothelial cells). We next treated primary mouse peritoneal mesothelial cells (pan-cytokeratin and intercellular adhesion molecule 1 positive cells) with 50 or 100 ng/mL recombinant AIF-1, and evaluated the direct effects of AIF-1 on these cells in vitro. We found that exogenous AIF-1 treatment induced inflammation and oxidative stress in mesothelial cells. Apart from the augmented IL-6 and TNF-α secretion, the level of ROS was upregulated and the activity of anti-oxidative SOD was reduced in cells exposed to AIF-1. Moreover, AIF-1 simulation triggered the activation of NF-κB pathway-enhanced the conversion of IκB to phosphorylated IκB and promoted the translocation of NF-κB p65 from cytoplasm into nucleus. Additionally, AIF-1-evoked inflammation in peritoneal mesothelial cells was attenuated by the addition of NF-κB inhibitor (BAY 11-7082). In brief, this study provides us novel information to understand the molecular regulation mechanisms of AIF-1 in peritoneal fibrosis.
腹膜透析（PD）常用于治疗终末期肾病患者，其长期并发症包括过度炎症和氧化应激。同种异体炎症因子 1（AIF-1）作为一种细胞质蛋白，最初从浸润的巨噬细胞中被识别出来，它与除巨噬细胞以外的细胞如内皮细胞和血管平滑肌细胞中的炎症有关。为了阐明 AIF-1 调节 PD 期间腹膜病理变化的分子机制，我们首先检测了 PD 小鼠腹膜组织中的 AIF-1 表达。结果显示，促纤维化刺激导致 AIF-1 上调，并触发腹膜组织炎症，并且 AIF-1 与细胞角蛋白（腹膜间皮细胞的标志物）共表达。接下来，我们用 50 或 100ng/ml 重组 AIF-1 处理原代小鼠腹膜间皮细胞（细胞角蛋白和细胞间黏附分子 1 阳性细胞），并在体外评估 AIF-1 对这些细胞的直接作用。我们发现外源性 AIF-1 处理诱导间皮细胞炎症和氧化应激。除了 IL-6 和 TNF-α 分泌增加外，ROS 水平上调，暴露于 AIF-1 的细胞中抗氧化 SOD 的活性降低。此外，AIF-1 模拟触发 NF-κB 通路的激活-增强 IκB 向磷酸化 IκB 的转化，并促进 NF-κB p65 从细胞质向核内转位。此外，NF-κB 抑制剂（BAY 11-7082）可减轻 AIF-1 诱导的腹膜间皮细胞炎症。总之，这项研究为我们提供了新的信息，以了解 AIF-1 在腹膜纤维化中的分子调控机制。
