Role of allograft inflammatory factor-1 in the regulation of inflammation and oxidative stress in primary peritoneal mesothelial cells
Role of allograft inflammatory factor-1 in the regulation of inflammation and oxidative stress in primary peritoneal mesothelial cells
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同种异体移植物炎症因子-1在原代腹膜间皮细胞炎症和氧化应激调节中的作用
DOI：
10.1002/cbin.11115
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发表时间：
2019
影响因子：
3.9
通讯作者：
Hao Lirong
中科院分区：
文献类型：
--
作者：
Zhou Yinan;Li Xin;Yuan Xueying;Hao Lirong
腹膜透析（PD）通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。同种异体移植物炎性因子1（AIF-1），作为一种细胞质蛋白，最初从浸润的巨噬细胞中鉴定出来，它与巨噬细胞以外的细胞（如内皮细胞和血管平滑肌细胞）中的炎症相关。为了阐明PD期间AIF-1调节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AIF-1的表达。结果显示，促纤维化刺激导致AIF-1上调并引发腹膜组织中的炎症，并且AIF-1与泛细胞角蛋白（腹膜间皮细胞的标志物）共表达。接下来，我们用50或100 ng/mL重组AIF-1处理原代小鼠腹膜间皮细胞（泛细胞角蛋白和细胞间粘附分子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治疗诱导间皮细胞的炎症和氧化应激。除了IL-6和TNF-α分泌增加外，暴露于AIF-1的细胞中ROS水平上调，抗氧化SOD活性降低。此外，AIF-1模拟触发了NF-κB途径的激活，增强了IκB向磷酸化IκB的转化，并促进NF-κB p65从细胞质移位到细胞核。此外，通过加入NF-κB抑制剂（BAY 11-7082），腹膜间皮细胞中AIF-1诱发的炎症减弱。总之，这项研究为我们了解AIF-1在腹膜纤维化中的分子调控机制提供了新的信息。
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.