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(American Journal of Pathology. 2006;169:1294-1302.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060185

Tumor Necrosis Factor-{alpha} and Interleukin-1ß Regulate Interleukin-8 Expression in Third Trimester Decidual Cells

Implications for the Genesis of Chorioamnionitis

Charles J. Lockwood*, Felice Arcuri{dagger}, Paolo Toti{dagger}, Claudio De Felice{ddagger}, Graciela Krikun*, Seth Guller*, Lynn F. Buchwalder* and Frederick Schatz*

From the Department of Obstetrics,* Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut; Department of Human Pathology and Oncology,{dagger} University of Siena, Siena, Italy; and Department of Pediatrics,{ddagger} 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-{alpha} (TNF-{alpha}) 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-{alpha} 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-{alpha} 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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