Viral ssRNA induces first trimester trophoblast apoptosis through an inflammatory mechanism.

Viral ssRNA induces first trimester trophoblast apoptosis through an inflammatory mechanism.
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DOI:
10.1111/j.1600-0897.2010.00817.x
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发表时间:
2010-07-01
期刊:
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子:
--
通讯作者:
Abrahams VM
Abrahams VM
中科院分区:
其他
文献类型:
--
作者:
Aldo PB;Mulla MJ;Romero R;Mor G;Abrahams VM

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怀孕期间的感染是造成流动性和死亡的一个重要原因。虽然病毒构成了重大威胁,但人们对它们对早孕的影响或相关机制知之甚少。本研究的目的是表征暴露于病毒ssRNA后滋养层的反应。用或不用病毒ssRNA处理妊娠早期滋养层细胞。通过多重分析和ELISA测量细胞因子的产生。使用Hoescht染色、细胞活力和caspase活性测定来确定细胞凋亡。用病毒ssRNA处理滋养层增加了它们的IL-8、IL-6和IFNβ的分泌。然而,ssRNA也诱导滋养层细胞凋亡。为了测试病毒ssRNA诱导的炎症反应是否是导致这种细胞凋亡诱导的原因,将来自滋养层的条件培养基(CM)加入到新鲜的细胞培养物中。来自病毒ssRNA处理的CM比对照CM诱导更高水平的滋养层细胞凋亡。此外,重组干扰素β可诱导滋养细胞凋亡。我们证明,病毒ssRNA诱导的促炎和I型干扰素反应的滋养层,这种炎症过程可能间接诱导滋养层细胞凋亡。这些结果提供了一种新的机制,通过这种机制,某些病毒感染可能会损害胎盘的完整性和功能,从而影响妊娠结局。
Infection during pregnancy represents a significant cause of mobility and mortality. While viruses pose a major threat, little is known about their effect on early pregnancy, or the mechanisms involved. The objective of this study was to characterize the trophoblast response following exposure to viral ssRNA. First trimester trophoblast cells were treated with or without viral ssRNA. Cytokine production was measured by multiplex analysis and ELISA. Apoptosis was determined using Hoescht staining, cell viability, and caspase activity assays. Treatment of trophoblasts with viral ssRNA increased their secretion of IL-8, IL-6 and IFNβ. However, the ssRNA also induced trophoblast apoptosis. To test whether the viral ssRNA-induced inflammatory response was responsible for this induction of apoptosis, conditioned media (CM) from trophoblasts was added to a fresh culture of cells. The CM from viral ssRNA-treated induced higher levels of trophoblast apoptosis than the control CM. Moreover, recombinant IFNβ induced trophoblast apoptosis. We demonstrate that viral ssRNA induces a pro-inflammatory and type I interferon response in the trophoblast, and that this inflammatory process may indirectly induce trophoblast apoptosis. These results provide a novel mechanism by which certain viral infections might compromise placental integrity and function, and therefore, pregnancy outcome.
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