| Autor: |
Qi, Chen, Limei, Chen, Bonnia, Liu, Chez, Vialli, Peter, Stone, Lai-Ming, Ching, Lawrence, Chamley |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
The Journal of pathology. 221(1) |
| ISSN: |
1096-9896 |
| Popis: |
Pre-eclampsia is a disorder of pregnancy characterized by hypertension and endothelial cell dysfunction. The causes of pre-eclampsia are unclear but it is proposed that a factor released from the placenta triggers the maternal symptoms. One possible triggering factor is dead trophoblasts that are shed from the placenta, then deported to become trapped in the maternal pulmonary capillaries. It is hypothesized that trophoblasts die by apoptosis in normal pregnancy, but by necrosis in pre-eclampsia. Deported trophoblasts may be phagocytosed by the pulmonary endothelial cells and we have previously shown that phagocytosis of necrotic trophoblasts leads to the activation of endothelial cells, accompanied by the release of interleukin-6 from these cells. However, the mechanistic pathway linking phagocytosis of necrotic trophoblasts and endothelial cell activation is unknown. Here we show that, after phagocytosis of necrotic, but not apoptotic, trophoblasts, endothelial cells secrete TGFbeta1. Using recombinant endoglin to inhibit the function of TGFbeta1 we have shown that the TGFbeta1 does not directly activate endothelial cells but rather it induces endothelial IL-6 secretion. The IL-6 then induces endothelial cell activation. Inhibiting either TGFbeta1 or IL-6 prevented endothelial cell activation in response to phagocytosing necrotic trophoblasts, but inhibiting IL-6 did not prevent secretion of TGFbeta1, confirming the order of signalling. IL-6 also reduced endothelial cell-surface endoglin but increased the amount of soluble endoglin released from placental explants. These interactions between the IL-6 and TGFbeta1 pathways in both the endothelium and placenta may help to regulate the maternal response to deported trophoblasts in pregnancy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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