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(American Journal of Pathology. 2006;168:445-452.)
© 2006 American Society for Investigative Pathology

Regulation of Monocyte Chemoattractant Protein-1 Expression by Tumor Necrosis Factor-{alpha} and Interleukin-1ß in First Trimester Human Decidual Cells

Implications for Preeclampsia

Charles J. Lockwood*, Paul Matta*, Graciela Krikun*, Louise A. Koopman{dagger}, Rachel Masch{ddagger}, Paolo Toti§, Felice Arcuri§, Se-Te Joseph Huang*, Edmund F. Funai* and Frederick Schatz*

From the Department of Obstetrics, Gynecology, and Reproductive Sciences,* Yale University School of Medicine, New Haven, Connecticut; the Department of Oncology,{dagger} Biogen Incorporated, Cambridge Massachusetts; the Department of Obstetrics and Gynecology,{ddagger} New York University School of Medicine, New York, New York; and the Department of Human Pathology and Oncology,§ University of Siena, Siena, Italy

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)-1ß. 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-1ß 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-1ß 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-1ß 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.




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