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

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.