title: Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha and interleukin-1beta in first trimester human decidual cells: implications for preeclampsia.
abstract: The current study describes a statistically significant increase in macrophages (CD68-positive cells) in the decidua of preeclamptic patients. To elucidate the regulation of this monocyte infiltration, expression of monocyte chemoattractant protein-1 (MCP-1) was assessed in leukocyte-free first trimester decidual cells. Confluent decidual cells were primed for 7 days in either estradiol or estradiol plus medroxyprogesterone acetate to mimic the decidualizing steroidal milieu of the luteal phase and early pregnancy. The medium was exchanged for a serum-free defined medium containing corresponding steroids +/- tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta. After 24 hours, enzyme-linked immunosorbent assay measurements indicated that the addition of medroxyprogesterone acetate did not affect MCP-1 output, whereas 10 ng/ml of TNF-alpha or IL-1beta increased output by 83.5-fold +/- 20.6 and 103.1-fold +/- 14.7, respectively (mean +/- SEM, n = 8, P < 0.05). Concentration-response comparisons revealed that even 0.01 ng/ml of TNF-alpha or IL-1beta elevated MCP-1 output by more than 15-fold. Western blotting confirmed the enzyme-linked immunosorbent assay results, and quantitative reverse transcriptase-polymerase chain reaction confirmed corresponding effects on MCP-1 mRNA levels. The current study demonstrates that TNF-alpha and IL-1beta enhance MCP-1 in first trimester decidua. This finding suggests a mechanism by which recruitment of excess macrophages to the decidua impairs endovascular trophoblast invasion, the primary placental defect of preeclampsia.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lockwood
authors.forename: Paul
authors.initials: P
authors.lastname: Matta
authors.forename: Graciela
authors.initials: G
authors.lastname: Krikun
authors.forename: Louise A
authors.initials: LA
authors.lastname: Koopman
authors.forename: Rachel
authors.initials: R
authors.lastname: Masch
authors.forename: Paolo
authors.initials: P
authors.lastname: Toti
authors.forename: Felice
authors.initials: F
authors.lastname: Arcuri
authors.forename: Se-Te Joseph
authors.initials: ST
authors.lastname: Huang
authors.forename: Edmund F
authors.initials: EF
authors.lastname: Funai
authors.forename: Frederick
authors.initials: F
authors.lastname: Schatz
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008183:Luteal Phase / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018932:Chemokine CCL2; D016895:Culture Media, Serum-Free; D004338:Drug Combinations; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D017258:Medroxyprogesterone Acetate