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.


METHODS
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.


CONCLUSIONS
MCP-1 protein expression is up regulated by thrombin in decidual cells across gestation, but not in stromal cells from predecidualized cycling endometrium.
Matta
Paul
P
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
Lockwood
Charles J
CJ
Schatz
Frederick
F
Krikun
Graciela
G
Rahman
Mizanur
M
Buchwalder
Lynn
L
Norwitz
Errol R
ER
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D003656:Decidua / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D047929:Term Birth; D013917:Thrombin / Q000502:physiology*
D018932:Chemokine CCL2; D013917:Thrombin