Surfactant Proteins SP-A and SP-D Modulate Uterine Contractile Events in ULTR Myometrial Cell Line.
Surfactant Proteins SP-A and SP-D Modulate Uterine Contractile Events in ULTR Myometrial Cell Line.
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DOI：
10.1371/journal.pone.0143379
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Karteris E
中科院分区：
文献类型：
--
作者：
Sotiriadis G;Dodagatta-Marri E;Kouser L;Alhamlan FS;Kishore U;Karteris E
肺表面活性物质蛋白SP-A和SP-D是模式识别先天免疫分子。然而，也有肺外存在，特别是在羊水和胎儿-母亲界面。有足够的证据表明SP-A和SP-D参与分娩的开始。这一点非常重要，因为早产与死亡率和发病率增加有关。在这项研究中，我们研究了重组形式的SP-A和SP-D（rhSP-A和rhSP-D，包括三聚体凝集素结构域）在体外收缩事件的影响，使用人子宫肌细胞系（ULTR）作为实验模型。用rhSP-A或rhSP-D处理增加ULTR细胞的细胞速度、移动距离和位移。rhSP-A和rhSP-D也影响ULTR在胶原基质上生长时的收缩反应，显示表面积减少。我们通过测量收缩相关蛋白（CAP）基因进一步研究了这种效应。用rhSP-A和rhSP-D处理诱导催产素受体（OXTR）和连接蛋白43（CX 43）的表达。此外，rhSP-A和rhSP-D还能诱导GROα和IL-8的分泌。rhSP-D还可诱导IL-6和IL-6 Ra的表达。我们提供的证据表明，SP-A和SP-D发挥了关键作用，在劳动前的调制事件，通过重新调节人类子宫肌层和诱导CAP基因和促炎细胞因子，从而将子宫从静止状态的收缩。
Pulmonary surfactant proteins SP-A and SP-D are pattern recognition innate immune molecules. However, there is extrapulmonary existence, especially in the amniotic fluid and at the feto-maternal interface. There is sufficient evidence to suggest that SP-A and SP-D are involved in the initiation of labour. This is of great importance given that preterm birth is associated with increased mortality and morbidity. In this study, we investigated the effects of recombinant forms of SP-A and SP-D (rhSP-A and rhSP-D, the comprising of trimeric lectin domain) on contractile events in vitro, using a human myometrial cell line (ULTR) as an experimental model. Treatment with rhSP-A or rhSP-D increased the cell velocity, distance travelled and displacement by ULTR cells. rhSP-A and rhSP-D also affected the contractile response of ULTRs when grown on collagen matrices showing reduced surface area. We investigated this effect further by measuring contractility-associated protein (CAP) genes. Treatment with rhSP-A and rhSP-D induced expression of oxytocin receptor (OXTR) and connexin 43 (CX43). In addition, rhSP-A and rhSP-D were able to induce secretion of GROα and IL-8. rhSP-D also induced the expression of IL-6 and IL-6 Ra. We provide evidence that SP-A and SP-D play a key role in modulating events prior to labour by reconditioning the human myometrium and in inducing CAP genes and pro-inflammatory cytokines thus shifting the uterus from a quiescent state to a contractile one.