Thrombin regulates monocyte chemoattractant protein-1 expression in human first trimester and term decidual cells

被引:22
作者
Matta, Paul [1 ]
Lockwood, Charles J. [1 ]
Schatz, Frederick [1 ]
Krikun, Graciela [1 ]
Rahman, Mizanur [1 ]
Buchwalder, Lynn [1 ]
Norwitz, Errol R. [1 ]
机构
[1] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA
基金
美国国家卫生研究院;
关键词
decidua; endometrium; monocyte chemoattractant protein-1; preeclampsia; pregnancy; thrombin;
D O I
10.1016/j.ajog.2006.09.008
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Objective: Excess decidual macrophage infiltration has been linked to preeclampsia and a failure of endovascular trophoblast invasion. Severe preeclampsia with shallow placentation has also been linked to acquired and inherited maternal thrombophilias and recurrent decidual hemorrhage, which generates thrombin from decidual cell-expressed tissue factor. Therefore, the current study evaluated whether thrombin affects monocyte chemoattractant protein-1 (MCP-1) expression in stromal cells that are derived from cycling and gestational endometrium. Study Design: Stromal cells that are isolated from cycling endometrium and first trimester and term decidua were grown to confluence, treated for 7 days with 10-8 mol/L estradiol (E2) + 10-7 mol/L medroxyprogesterone acetate (MPA), then switched to a serum-free medium that contained the corresponding steroids ± thrombin. MCP-1 protein release was measured by enzyme-linked immunosorbent assay and Western blot; MCP-1 messenger RNA levels were assessed by real-time quantitative reverse transcription-polymerase chain reaction. Results: Secreted MCP-1 levels were not significantly different in stromal or decidual cell cultures that were incubated with E2 or with E2 + MPA. Thrombin increased immunoreactive MCP-1 expression in a dose-response fashion in first trimester and term decidual cells but not in endometrial stromal cells. Thrombin-induced MCP-1 protein output was unaffected by MPA but was abrogated by incubation with the thrombin inhibitor, hirudin. Unexpectedly, thrombin-enhanced MCP-1 protein expression was unaccompanied by corresponding changes in steady state MCP-1 messenger RNA levels, which suggests its effects were posttranslational. Conclusion: MCP-1 protein expression is up regulated by thrombin in decidual cells across gestation, but not in stromal cells from predecidualized cycling endometrium. © 2007 Mosby, Inc. All rights reserved.
引用
收藏
页码:268 / 270
页数:3
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