PMID- 17346550 OWN - NLM STAT- MEDLINE DCOM- 20070503 LR - 20071203 IS - 1097-6868 (Electronic) IS - 0002-9378 (Linking) VI - 196 IP - 3 DP - 2007 Mar TI - Thrombin regulates monocyte chemoattractant protein-1 expression in human first trimester and term decidual cells. PG - 268.e1-8 AB - 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. FAU - Matta, Paul AU - Matta P AD - Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA. FAU - Lockwood, Charles J AU - Lockwood CJ FAU - Schatz, Frederick AU - Schatz F FAU - Krikun, Graciela AU - Krikun G FAU - Rahman, Mizanur AU - Rahman M FAU - Buchwalder, Lynn AU - Buchwalder L FAU - Norwitz, Errol R AU - Norwitz ER LA - eng GR - R01-HL070004-03/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Am J Obstet Gynecol JT - American journal of obstetrics and gynecology JID - 0370476 RN - 0 (Chemokine CCL2) RN - EC 3.4.21.5 (Thrombin) SB - IM MH - Cells, Cultured MH - Chemokine CCL2/*biosynthesis MH - Decidua/*cytology/*metabolism MH - Female MH - Humans MH - Pregnancy MH - Pregnancy Trimester, First MH - Term Birth MH - Thrombin/*physiology EDAT- 2007/03/10 09:00 MHDA- 2007/05/04 09:00 CRDT- 2007/03/10 09:00 PHST- 2006/03/28 00:00 [received] PHST- 2006/07/08 00:00 [revised] PHST- 2006/09/14 00:00 [accepted] PHST- 2007/03/10 09:00 [pubmed] PHST- 2007/05/04 09:00 [medline] PHST- 2007/03/10 09:00 [entrez] AID - S0002-9378(06)01203-8 [pii] AID - 10.1016/j.ajog.2006.09.008 [doi] PST - ppublish SO - Am J Obstet Gynecol. 2007 Mar;196(3):268.e1-8. doi: 10.1016/j.ajog.2006.09.008.