| Preeclampsia is one of the common diseases of pregnancy which affecting 3-5% of pregnancy women. It is the major cause of maternal mortality and morbidity. Although the pathogenesis of preeclampsia is unclear it is proposed placental and maternal factors contribute to its pathogenesis. One possible placental factor is dead trophoblasts that are shed from the placenta then deported to become trapped in the maternal pulmonary capillaries. It is hypothesised that in normal pregnancy trophoblasts die by apoptosis but by necrosis in preeclampsia. Deported trophoblasts are phagocytosed by endothelial cells and we have previously shown that phagocytosis of necrotic trophoblasts leads to the activation of endothelial cells. In clinically established preeclampsia, maternal circulating levels of cytokines, such as TGFβ,1L-6 and TNF alpha are reported to be elevated. This study investigates whether cytokines can alter the shedding of apoptotic material to necrotic materials from the placenta. To investigate this question, placental explants were treated with nine cytokines which resulted in significantly increased amounts of trophoblasts being shed from explants treated with IL-6, TGFβ1 or TNFαbut not the other cytokines. Trophoblasts shed from explants treated with IL-6, or TGFβ1, TGFβ3 demonstrated a significant reduction in the activities of caspases 3&7. While exposing endothelial cells to trophoblasts shed from explants treated with IL-6, TGF p 1 or TNFαresulted in endothelial cell activation. IL-6 and TGFβ1's such effect can be blocked by verapamil. These results suggest that some cytokines can induce excess and/or aberrant death (necrotic or aponecrotic) trophoblast death. In addition, IL-6 increased the amount of sEndoglin secretion from placenta explants. It reflected in vivo this might explain, at least in part, how cytokines could affect trophoblast shedding/deportation and contribute to the pathogenesis of preeclampsia. |
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