病毒 ssRNA 通过炎症机制诱导早期妊娠滋养层细胞凋亡。
Viral ssRNA induces first trimester trophoblast apoptosis through an inflammatory mechanism.
机构信息
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University, School of Medicine, New Haven, CT 06510, USA.
出版信息
Am J Reprod Immunol. 2010 Jul 1;64(1):27-37. doi: 10.1111/j.1600-0897.2010.00817.x. Epub 2010 Feb 17.
PROBLEM
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.
METHOD OF STUDY
First trimester trophoblast cells were treated with or without viral ssRNA. Cytokine production was measured using multiplex analysis and ELISA. Apoptosis was determined using Hoechst staining, cell viability, and caspase activity assays.
RESULTS
Treatment of trophoblasts with viral ssRNA increased their secretion of IL-8, IL-6, and IFNbeta. 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 were 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 IFNbeta induced trophoblast apoptosis.
CONCLUSION
We demonstrate that viral ssRNA induces a pro-inflammatory and type I interferon response in the trophoblast and 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.
问题
怀孕期间的感染是导致母婴发病率和死亡率的重要原因。病毒是一个主要威胁,但对于其对早期妊娠的影响以及涉及的机制知之甚少。本研究旨在描述病毒 ssRNA 暴露后滋养层的反应。
研究方法
用或不用病毒 ssRNA 处理妊娠早期滋养层细胞。采用多重分析和 ELISA 检测细胞因子的产生。用 Hoechst 染色、细胞活力和半胱天冬酶活性测定法测定细胞凋亡。
结果
用病毒 ssRNA 处理滋养层细胞增加了 IL-8、IL-6 和 IFNβ 的分泌。然而,ssRNA 也诱导了滋养层细胞凋亡。为了测试病毒 ssRNA 诱导的炎症反应是否是诱导凋亡的原因,将滋养层细胞的条件培养基(CM)加入新鲜的细胞培养物中。用病毒 ssRNA 处理的 CM 诱导的滋养层细胞凋亡水平高于对照 CM。此外,重组 IFNβ 诱导了滋养层细胞凋亡。
结论
我们证明病毒 ssRNA 在滋养层中诱导了促炎和 I 型干扰素反应,这一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,即某些病毒感染可能损害胎盘的完整性和功能,从而影响妊娠结局。