Hyperglycemia induces inflammatory mediators in the human chorionic villous
Hyperglycemia induces inflammatory mediators in the human chorionic villous
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DOI：
10.1016/j.cyto.2018.07.020
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发表时间：
2018-11-01
期刊：
影响因子：
3.8
通讯作者：
Calderon, Iracema M. P.
中科院分区：
文献类型：
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作者：
Correa-Silva, Simone;Alencar, Aline P.;Calderon, Iracema M. P.
这项研究是基于这样的假设，即IL-1 β及其中枢调节因子炎性体可能在不同妊娠期高血糖水平母亲的胎盘组织所表现出的炎症状态中发挥作用。根据血糖参考值将孕妇分为非糖尿病（n = 15）、轻度妊娠期高血糖（n = 15）、妊娠期糖尿病（n = 15）和2型糖尿病（n = 15）。我们研究了母体血浆和胎盘组织中促炎因子的水平（通过ELISA或免疫组织化学）和绒毛中NF κ B活性（通过电泳迁移率变动分析）和炎性体蛋白表达（通过Western印迹）。在所有高血糖条件下，母体血浆和胎盘炎症因子（IL-1 β、IL-6和MCP-1）水平均升高。绒毛间质细胞对CD 68呈强免疫反应性。此外，与合体滋养层，绒毛间质细胞也被染色，以检测iNOS，MCP-1，TLR 2，和TLR 4。虽然蛋白质水平在各组中波动，但NLRP 1，NLRP 3，ASC和Caspase 1在所有高血糖组中均上调，表明炎性小体可能在这些孕妇中组装。在高血糖组中，NF κ B活性也表现出更高的水平，这可能意味着促炎细胞因子的产生。总之，妊娠期间母体葡萄糖水平升高改变了全身和胎盘炎症模式，这与炎性体因子的表达以及促炎细胞因子IL-1 β的加工和分泌平行发生。这些结果表明，在所有妊娠期高血糖状况中，甚至在比妊娠期或显性糖尿病严重程度低的高血糖中，炎症状况可能与炎性小体激活和炎性细胞因子分泌相关。炎症体激活作为炎症因子的可能来源，可能是管理高血糖和预防不良妊娠结局时需要考虑的重要目标。
This study was based on the hypothesis that IL-1 beta and its central regulator, the inflammasome, may play a role in the inflammatory condition exhibited by placental tissues from mothers with different gestational hyperglycemia levels. Pregnant women were classified according to the glycemic reference as non-diabetic (n = 15), mild gestational hyperglycemia (n = 15), gestational diabetes mellitus (n = 15) and type 2 diabetes mellitus (n = 15). We investigated levels of pro-inflammatory factors in maternal plasma and placental tissues (by ELISA or immunohistochemistry) and, NFKB activity (by electrophoretic mobility shift assay) and inflammasome protein expression (by Western blot) in chorionic villous. Maternal plasma and placental levels of inflammatory factors (IL-1 beta, IL-6, and MCP-1) were increased during all hyperglycemic conditions. Villous stroma cells showed strong immunoreactivity to CD68. In addition, with syncytiotrophoblast, the villous stroma cells were also stained to detect iNOS, MCP-1, TLR2, and TLR4. Although the levels of protein had fluctuated in the groups, NLRP1, NLRP3, ASC, and Caspase 1 were up-regulated in all hyperglycemic groups suggesting the inflammasome may be assembled in these pregnant women. The NFKB activity also exhibited higher levels in hyperglycemic groups, which might imply in pro-inflammatory cytokines production. In summary, increased maternal glucose levels during pregnancy changed systemic and placental inflammatory patterns, which occurred in parallel with the expression of inflammasome factors and processing and secretion of the pro-inflammatory cytokine IL-1 beta. These results suggest an inflammatory condition in all gestational hyperglycemic conditions, even in hyperglycemia that is less severe than gestational or overt diabetes, likely associated with inflammasome activation and inflammatory cytokine secretion. Inflammasome activation as a possible source of inflammatory factors may be an important target to be considered while managing hyperglycemia and preventing adverse pregnancy outcomes.