Liong Stella, Lappas Martha
Mercy Perinatal Research Centre, Mercy Hospital for Women, 4th Floor, 163 Studley Road, Heidelberg, Vic. 3084, Australia.
Reprod Fertil Dev. 2018 Jan;30(2):313-329. doi: 10.1071/RD17081.
Preterm birth remains one of the leading causes of neonatal death. Inflammation and maternal infection are two of the leading aetiological factors for preterm birth. Labour is associated with increased production of proinflammatory cytokines, chemokines and prolabour mediators in human gestational tissues. In non-gestational tissues, synthesis of proinflammatory and prolabour mediators is regulated by components of the protein synthesis machinery. Therefore, in the present study we investigated the effect of human labour on the expression of three protein synthesis markers, namely eukaryotic elongation factor 2 kinase (EEF2K), mitogen-activated protein kinase interacting protein kinase 1 (MKNK1) and eukaryotic translation initiation factor 4E (EIF4E), and their role in regulating inflammation in human gestational tissues. In fetal membranes and myometrium, EEF2K expression was significantly lower, whereas MKNK1 expression was significantly higher withterm and preterm labourcompared to term nolabour. In contrast, EIF4E expression did not change in fetal membranes or myometrium with labour. In primary myometrial cells, loss-of-function studies using specific chemical inhibitors of EEF2K (A484954) and MKNK1 (CGP57380) demonstrated that MKNK1, but not EEF2K, was required for polyinosinic-polycytidylic acid (poly(I:C); a viral double-stranded RNA mimetic) and interleukin (IL)-1β-induced production of IL6, C-X-C motif chemokine ligand 8 (CXCL8), prostaglandin-endoperoxide synthase 2 (PTGS2) and prostaglandin F2α. In conclusion, spontaneous term and preterm labour is associated with decreased EEF2K and increased MKNK1 expression in fetal membranes and myometrium. Moreover, MKNK1 is involved in the genesis of proinflammatory and prolabour mediators that is mediated by inflammation or infection. However, further studies are required to elucidate the role of EEF2K in human labour.
早产仍然是新生儿死亡的主要原因之一。炎症和母体感染是早产的两个主要病因。分娩与人类妊娠组织中促炎细胞因子、趋化因子和促分娩介质的产生增加有关。在非妊娠组织中，促炎和促分娩介质的合成受蛋白质合成机制成分的调节。因此，在本研究中，我们调查了人类分娩对三种蛋白质合成标志物，即真核延伸因子2激酶（EEF2K）、丝裂原活化蛋白激酶相互作用蛋白激酶1（MKNK1）和真核翻译起始因子4E（EIF4E）表达的影响，以及它们在调节人类妊娠组织炎症中的作用。在胎膜和子宫肌层中，与足月未分娩相比，足月和早产时EEF2K表达显著降低，而MKNK1表达显著升高。相反，EIF4E表达在胎膜或子宫肌层中不因分娩而改变。在原代子宫肌层细胞中，使用EEF2K（A484954）和MKNK1（CGP57380）的特异性化学抑制剂进行的功能丧失研究表明，多聚肌苷酸-聚胞苷酸（poly(I:C)；一种病毒双链RNA模拟物）和白细胞介素（IL）-1β诱导的IL6、C-X-C基序趋化因子配体8（CXCL8）、前列腺素内过氧化物合酶2（PTGS2）和前列腺素F2α的产生需要MKNK1，而不是EEF2K。总之，足月和早产与胎膜和子宫肌层中EEF2K降低和MKNK1表达增加有关。此外，MKNK1参与由炎症或感染介导的促炎和促分娩介质的产生。然而，需要进一步研究以阐明EEF2K在人类分娩中的作用。
