IL-6、TNFα和TGFβ可促进非凋亡性滋养细胞脱落并进而导致内皮细胞活化

Preeclampsia is a complex disease of pregnancy with both feto-placental and maternal factors contributing to its pathogenesis. Failed transformation of the uterine spiral arteries leading to release of ischemic placental factors into the maternal circulation is thought to be the initial step in triggering preeclampsia. One placental factor associated with preeclampsia is necrotic trophoblastic debris that is deported in the maternal blood. The deported material ranges from multinucleated syncytial knots to nano-meter scale exosomes. Increasingly, it is being questioned whether failed transformation of the spiral arteries with subsequent placental ischemia is either necessary, or adequate, to explain the genesis of preeclampsia. In clinically established preeclampsia, maternal circulating levels of cytokines, such as TGFβ, IL-6 and TNFα, are reported to be elevated. This study investigates whether cytokines can increase the shedding of necrotic material 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, TGFβ-1 or TNFα but not the other cytokines. Trophoblasts shed from explants treated with IL-6, or TGFβ-1 demonstrated a significant reduction in the activities of caspases while exposing endothelial cells to trophoblasts shed from explants treated with IL-6, TGF β1 or TNFα resulted in endothelial cell activation. These results suggest that some cytokines can induce excess and/or aberrant death (necrotic or aponecrotic) trophoblast death. If reflected in vivo this might explain, at least in part, how some cytokines could affect trophoblast shedding/deportation and contribute to the pathogenesis of preeclampsia. © 2009 Elsevier Ltd. All rights reserved.