Szukiewicz Dariusz, Pyzlak Michal, Szewczyk Grzegorz, Stangret Aleksandra, Trojanowski Seweryn, Bachanek Michal, Braksator Wojciech, Wejman Jaroslaw
Department of General & Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Second Faculty of Medicine, Medical University of Warsaw, ul. Pawinskiego 3C, 02-106 Warsaw, Poland.
Department of Obstetrics & Gynecology, Second Faculty of Medicine, Medical University of Warsaw, ul. Kondratowicza 8, 03-242 Warsaw, Poland.
Mediators Inflamm. 2017;2017:9853108. doi: 10.1155/2017/9853108. Epub 2017 Jun 1.
Hyperglycemia-induced hyperactivity of chemokine CX3CL1 (fractalkine) occurs in the human placenta. Anti-inflammatory/antioxidant activities of resveratrol (3,5,4'-trihydroxy--stilbene) are related to the modulation of chemokine CX3CL1 and its receptor, CX3CR1, signaling pathways. We examined the influence of high glucose (25 mmol/L glucose; HG group; = 36) on resveratrol-mediated effects on CX3CL1 and TNF- production by the placental lobule, CX3CR1 expression and contents of CX3CR1, TNF- receptor 1 (TNFR1), and NF-B proteins in placental tissue. The placental lobules perfused under normoglycemic conditions formed the control NG group ( = 36). Resveratrol (50 and 100 M; subgroups B and C) administered into the perfusion fluid lowered the production of both CX3CL1 and TNF-. The reductions in CX3CL1 levels were more evident in the NG group. CX3CR1 expression was significantly higher in the NG subgroups B and C compared to the HG subgroups B and C (385.2 and 426.5% versus 199.3 and 282.4%, resp.). An increase in CX3CR1 protein content in placental lysates was observed in the NG subgroups B and C. Also, resveratrol significantly decreased NF-Bp65 protein content only in the NG group, not affecting hyperglycemia-elicited TNFR1 upregulation. In conclusion, euglycemia assures optimal effects of resveratrol pertaining to CX3CL1/CX3CR1 signaling in the placenta. Future studies on resveratrol are needed, especially those including maternal-fetal risk assessments.
高血糖诱导的趋化因子CX3CL1（分形趋化因子）的活性增强发生在人胎盘中。白藜芦醇（3,5,4'-三羟基芪）的抗炎/抗氧化活性与趋化因子CX3CL1及其受体CX3CR1信号通路的调节有关。我们研究了高糖（25 mmol/L葡萄糖；HG组；n = 36）对白藜芦醇介导的胎盘小叶CX3CL1和TNF-α产生、CX3CR1表达以及胎盘组织中CX3CR1、TNF-α受体1（TNFR1）和NF-κB蛋白含量的影响。在正常血糖条件下灌注的胎盘小叶形成对照组NG组（n = 36）。向灌注液中加入白藜芦醇（50和100 μM；B组和C组亚组）可降低CX3CL1和TNF-α的产生。CX3CL1水平的降低在NG组中更为明显。与HG组的B组和C组亚组相比，NG组的B组和C组亚组中CX3CR1表达显著更高（分别为385.2%和426.5%对199.3%和282.4%）。在NG组的B组和C组亚组中观察到胎盘裂解物中CX3CR1蛋白含量增加。此外，白藜芦醇仅在NG组中显著降低NF-κBp65蛋白含量，而不影响高血糖引起的TNFR1上调。总之，正常血糖可确保白藜芦醇在胎盘中对CX3CL1/CX3CR1信号传导产生最佳作用。需要对白藜芦醇进行进一步研究，尤其是那些包括母婴风险评估的研究。
