Ryu Byung Jun, Han Jae Won, Kim Ryang Hee, Yun Sohyun, Kim Tae Hyun, Hur Sung Eun, Kim Chul Jung, Lee Sung Ki
Department of Obstetrics and Gynecology, College of Medicine, Myunggok Medical Research Center, Konyang University, Daejeon, Korea.
Am J Reprod Immunol. 2017 Aug;78(2). doi: 10.1111/aji.12672. Epub 2017 Mar 22.
Decidual stromal cells (DSCs) are known to regulate trophoblast invasion via unveiled mechanism yet. And nucleotide-binding oligomerization domain-containing protein 1 (NOD1) may influence on this DSC-trophoblast interaction. We investigated the mechanism underlying the DSC-mediated regulation of trophoblast invasion and the effect of NOD1 on their cross talk. Using human primary DSCs, BeWo cell invasion was measured. Cytokine secretion and MAP kinase signaling were examined in DSCs following treatment with NOD1 agonist, Tri-DAP. DSCs secreted IL-8 and increased trophoblast invasion. Tri-DAP further increased IL-8 secretion from DSCs via JNK pathway and facilitated both MMP-2 production and trophoblast invasion compared with control. Upon cotreatment of IL-8 and anti-IL-8 antibody to BeWo cells, the number of invading trophoblasts and MMP-2 production decreased significantly. These results suggest that IL-8 from DSCs may play a role to increase the invasiveness of trophoblast cells into the decidua via NOD1/JNK pathway.
已知蜕膜基质细胞（DSCs）通过尚未明确的机制调节滋养层细胞的侵袭。含核苷酸结合寡聚化结构域蛋白1（NOD1）可能会影响这种DSC与滋养层细胞的相互作用。我们研究了DSC介导的滋养层细胞侵袭调节机制以及NOD1对它们之间相互作用的影响。使用人原代DSCs，检测BeWo细胞的侵袭情况。在用NOD1激动剂Tri-DAP处理后，检测DSCs中的细胞因子分泌和丝裂原活化蛋白激酶信号传导。DSCs分泌白细胞介素-8（IL-8）并增加滋养层细胞的侵袭。与对照组相比，Tri-DAP通过JNK途径进一步增加了DSCs中IL-8的分泌，并促进了基质金属蛋白酶-2（MMP-2）的产生和滋养层细胞的侵袭。在用IL-8和抗IL-8抗体共同处理BeWo细胞后，侵袭的滋养层细胞数量和MMP-2的产生显著减少。这些结果表明，来自DSCs的IL-8可能通过NOD1/JNK途径在增加滋养层细胞向蜕膜侵袭的过程中发挥作用。
