Interleukin-10 May Participate in Regulating Trophoblast Invasion in Human Placentae Throughout Gestation
American journal of reproductive immunology(2008)
摘要
ProblemA successful human pregnancy requires cytotrophoblasts from the fetal portion of the placenta to adopt tumor-like properties. But unlike tumor metastasis, cytotrophoblast invasion is highly regulated both spatially and temporally. The mechanisms that regulate human trophoblast invasion are understood poorly.Method of studyWith a view to obtain some findings on the mechanisms that regulate human trophoblast invasion, we applied the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) method to compare the expression of invasion-associated genes in cytotrophoblasts isolated from first- and third-trimester placental tissues.Results In trophoblast cells of first-trimester pregnancy, the mRNA contents of matrix metalloproteinase (MMP)-9 and urokinase-type plasminogen activator (uPA) were higher than that in the third-trimester cytotrophoblasts, while no difference of MMP-2 mRNA expression level was found between trophoblastic cells of different gestational ages. The expression level of plasminogen activator inhibitors-1 mRNA in first-trimester cytotrophoblasts was shown to be much lower than that in trophoblast cells prepared from third-trimester placental tissues. Furthermore, expression of both tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in cytotrophoblasts were significantly up-regulated in third-trimester when compared with the first-trimester of pregnancy. To further investigate the factors that caused the change of invasion-associated genes expression in trophoblast cells, we found that interleukin-10 (IL-10) could decrease the content of MMP-9 mRNA in cytotrophoblasts of first-trimester gestation, and the magnitude of suppression increased with increasing IL-10 concentration.ConclusionThe gradually reduced trophoblast invasion with gestational weeks might be on account of the change of proteolytic enzymes/activator/inhibitor genes expression. IL-10 could be one of the factors participating in the regulation of trophoblast invasion during gestational process.
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关键词
cytotrophoblast,interleukin-10,invasion,matrix metalloproteinase,plasminogen activator,tissue inhibitor of metalloproteinase
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