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and Interleukin-1ß Regulate Interleukin-8 Expression in Third Trimester Decidual Cells
From the Department of Obstetrics,* Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut; Department of Human Pathology and Oncology, University of Siena, Siena, Italy; and Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy
Chorioamnionitis is associated with intense neutrophil infiltration of the decidua. We therefore determined whether chorioamnionitis enhances decidual interleukin-8 (IL-8) expression and examined cytokine-regulated decidual IL-8 expression. Decidua from chorioamnionitis-complicated pregnancies, but not term controls, displayed marked IL-8 immunohistochemical staining and a dense neutrophil infiltrate. Reverse transcriptase-polymerase chain reaction of microdissected decidual cells identified IL-8 mRNA, confirming decidual synthesis of IL-8. Confluent leukocyte-free term decidual cells were primed with 10–8 mol/L estradiol (E2) or E2 + 10–7 mol/L medroxyprogesterone acetate to mimic the steroidal milieu of pregnancy. Compared with cultures maintained in E2 alone, E2 + medroxyprogesterone acetate neither significantly affected IL-8 levels nor altered the response to the cytokines. The addition of 1.0 ng/ml tumor necrosis factor-
(TNF-) or interleukin-1 ß (IL-1ß) increased IL-8 secretion levels by 236.6 ± 51.4- and 1062.6 ± 254.3-fold, respectively (n = 8, mean ± SEM, P < 0.05), as measured by enzyme-linked immunosorbent assay. Concentration-response studies revealed that 0.01 ng/ml TNF- and IL-1ß elevated IL-8 output by 10- and 100-fold, respectively. Western blotting confirmed these results, and quantitative reverse transcriptase-polymerase chain reaction demonstrated parallel changes in mRNA levels. In conclusion, IL-8 is strongly expressed in term decidua during chorioamnionitis, and TNF- and IL-1ß enhance IL-8 expression in term decidual cells, suggesting that these cytokines are important regulators of chorioamnionitis-related decidual neutrophil infil-tration.
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