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Anakinra and etanercept prevent embryo loss in pregnant nonobese diabetic mice

机译:Anakinra和etanercept可以预防怀孕的非肥胖糖尿病小鼠的胚胎丢失

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Bacteria and viruses activate the host innate immune response via Toll-like receptor (TLR)-involved signaling and potentially cause pregnancy failure. TLR7 and TLR9 respond to single-stranded RNA (a viral intermediate) and hypomethylated CpG DNA motifs (specific molecular constituents of bacteria) respectively. In this study, we treated murine RAW264.7 cells with R837, CpG1826, or a combination of the two. RT-PCR was performed to detect cytokines, Tlr7, and Tlr9. WT and nonobese diabetic murine embryo resorption models were established by i.p. injections of TLR7 and TLR9 ligands. Neutralizing antibodies and the IL1β and TNFα inhibitors were used. The specific inhibitors anakinra and etanercept effectively prevented TLR7 and TLR9 ligand-induced embryo loss. Notably, this effect was not observed in decidual NK cell-depleted mice. Our findings suggest that anakinra and etanercept may have potential for preventing TLR7 or TLR9 ligand-induced abortion in the presence of decidual NK cells.
机译:细菌和病毒通过涉及Toll样受体(TLR)的信号激活宿主固有的免疫反应,并可能导致妊娠失败。 TLR7和TLR9分别对单链RNA(一种病毒中间体)和低甲基化的CpG DNA基序(细菌的特定分子组成)作出反应。在这项研究中,我们用R837,CpG1826或两者的组合处理了鼠RAW264.7细胞。进行RT-PCR以检测细胞因子,Tlr7和Tlr9。通过ip建立WT和非肥胖糖尿病鼠胚胎吸收模型。 TLR7和TLR9配体的注射。使用了中和抗体以及IL1β和TNFα抑制剂。特异性抑制剂anakinra和etanercept有效地防止了TLR7和TLR9配体诱导的胚胎丢失。值得注意的是,在蜕膜NK细胞缺失的小鼠中未观察到这种作用。我们的研究结果表明,在蜕膜性NK细胞存在的情况下,anakinra和etanercept可能具有预防TLR7或TLR9配体诱导的流产的潜力。

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