Sosińska Patrycja, Baum Ewa, Maćkowiak Beata, Staniszewski Ryszard, Jasinski Tomasz, Umezawa Kazuo, Bręborowicz Andrzej
Department of Pathophysiology, Poznań University of Medical Sciences Poznań, Poland.
Department of Pathophysiology, Poznań University of Medical SciencesPoznań, Poland; Department of Bioethics, Poznań University of Medical SciencesPoland.
Am J Transl Res. 2016 Dec 15;8(12):5756-5765. eCollection 2016.
Peritoneal mesothelial cells exposed to bioincompatible dialysis fluids contribute to damage of the peritoneum during chronic dialysis. Inflammatory response triggered in the mesothelium leading to neovascularization and fibrosis plays an important role in that process. We studied the effects of Dehydroxymethyepoxyquinmicin (DHMEQ)-an NF-κB inhibitor on function of human peritoneal mesothelial cells (HPMC) in culture. DHMEQ studied in concentrations of 1-10 µg/ml was not toxic to HPMC. Synthesis of IL-6, MCP-1 and hyaluronan in unstimulated and stimulated with interleukin-1 (100 pg/ml) HPMC was inhibited in the presence of DHMEQ and the effect was proportional to the dose of the drug. DHMEQ (10 µg/ml) reduced in unstimulated HPMC synthesis of IL-6 (-55%), MCP-1 (-58%) and hyaluronan (-41%). Respective values for stimulated HMPC were: -63% for IL-6, -57% for MCP-1 and -67% for hyaluronan. The observed effects were due to the suppression of the expression of genes responsible for the synthesis of these molecules. DHMEQ modified the effects of the effluent dialysates from CAPD patients on the function of HMPC. Dialysate induced accelerated growth of these cells, and synthesis of collagen was inhibited in the presence of DHMEQ 10 µg/ml, by 69% and 40%, respectively. The results of our study show that DHMEQ effectively reduces inflammatory response in HMPC and prevents excessive dialysate induced proliferation and collagen synthesis in these cells. All of these effects may be beneficial during chronic peritoneal dialysis and prevents progressive dialysis-induced damage to the peritoneum.
暴露于生物不相容性透析液的腹膜间皮细胞在慢性透析过程中会导致腹膜损伤。间皮中引发的炎症反应导致新血管形成和纤维化，在这一过程中起重要作用。我们研究了NF-κB抑制剂去羟甲基环氧喹霉素（DHMEQ）对培养的人腹膜间皮细胞（HPMC）功能的影响。研究发现，浓度为1-10μg/ml的DHMEQ对HPMC无毒。在存在DHMEQ的情况下，未受刺激以及用白细胞介素-1（100 pg/ml）刺激的HPMC中IL-6、MCP-1和透明质酸的合成受到抑制，且该作用与药物剂量成正比。DHMEQ（10μg/ml）使未受刺激的HPMC中IL-6的合成减少了55%，MCP-1减少了58%，透明质酸减少了41%。受刺激的HMPC的相应数值分别为：IL-6减少63%，MCP-1减少57%，透明质酸减少67%。观察到的这些作用是由于负责这些分子合成的基因表达受到抑制。DHMEQ改变了持续性非卧床腹膜透析（CAPD）患者透析液对HMPC功能的影响。透析液可诱导这些细胞加速生长，而在存在10μg/ml DHMEQ的情况下，胶原蛋白合成分别被抑制了69%和40%。我们的研究结果表明，DHMEQ可有效降低HPMC中的炎症反应，并防止透析液诱导这些细胞过度增殖和胶原蛋白合成。所有这些作用在慢性腹膜透析期间可能是有益的，并可防止透析引起的腹膜进行性损伤。
