title: IL-6, TNFalpha and TGFbeta promote nonapoptotic trophoblast deportation and subsequently causes endothelial cell activation.
abstract: 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 TGFbeta, IL-6 and TNFalpha, 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, TGFbeta-1 or TNFalpha but not the other cytokines. Trophoblasts shed from explants treated with IL-6, or TGFbeta-1 demonstrated a significant reduction in the activities of caspases while exposing endothelial cells to trophoblasts shed from explants treated with IL-6, TGF beta1 or TNFalpha 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.
authors: Hospital of Obstetrics & Gynaecology, Fudan University, Shanghai, China.
authors: L M
authors: LM
authors: Chen
authors: B
authors: B
authors: Liu
authors: H B
authors: HB
authors: Zhao
authors: P
authors: P
authors: Stone
authors: Q
authors: Q
authors: Chen
authors: L
authors: L
authors: Chamley
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010920:Placenta / Q000166:cytology / Q000502:physiology; D011247:Pregnancy; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014327:Trophoblasts / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D014700:Verapamil; D020169:Caspases