the Implications of Pathogenesis of Pre-Eclampsia
Preeclampsia is a severe complication of human pregnancy. It occurs in 4-5% of all pregnancies and remains a leading cause of maternal and neonatal mortality and morbidity. The pathophysiology of this syndrome is not fully understood. Two theories are proposed to explain the development of preeclampsia: defective trophoblast invasion in the first trimester, and poor maternal immunoregulation against the fetus. Pro-inflammatory cytokines are induced in the second mechanism, with a subsequent generalized endothelial dysfunction in the mother. Interleukin-10 (IL-10) plays a major role in this pathway.
According to recent literature, debates still exist on the role of IL-10 in the pathogenesis of preeclampsia. IL-10 may increase immunoregulation (seemingly against the development of preeclampsia), but also prohibit the extravillous trophoblast invasion on the other hand (seemingly towards the development of preeclampsia). According to recent authoritative journals, the expression of IL-10 pre-eclamptic placenta is increased; but some other influential journals have the totally contrary results. We believe this diverse exhibition may be due to overlook the paracrine effect of decidual cells (representative of maternal environment), and in vitro cultured condition does not parallel to physiological condition.
Our experiment has first obtained the qualification of Ethical Committee of our hospital and the permission of the examined patients. We first collect the serum sample of preeclampsia patient and analyze the IL-10 level by ELISA kit, and compared with normal control. Then we isolate trophoblast from pre-eclamptic women and normal control. These trophoblasts are further treated with (1) co-cultured with decidual cell line (2) Lipofectamine transfection with IL-10 (overexpression of IL-10) (3) signal interference ribonucleotide (siRNA) of IL-10 (knockdown IL-10 function). Each groups (including trophoblast alone from patients or normal control) were subjected to the analysis of IL-10 mRNA amount by RT-PCR. Further experiments for these treated trophoblast are transwell migration assay and invasion assay, matrix metalloproteinase assay to determine the change of invasive capacity; and Fas ligand expression to determine the change of immunoregulation.
Our effort is not only to determine the role of IL-10 in the pathogenesis of preeclampsia, but also the development of siRNA IL-10 may give a light in the treatment of preeclampsia.
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||The Impact of Interleukin-10 in the Invasion Capacity and Immunoregulation During Pregnancy: the Implications of Pathogenesis of Pre-Eclampsia.|
|Study Start Date:||January 2004|
|Study Completion Date:||January 2009|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00154934
|Taipei, Taiwan, 10016|
|Study Chair:||Yang Pan-Chyr||National Taiwan University Hospital Research Ethics Committee|