Abstract
Problem: IL-18 is a novel cytokine, which promotes inflammation and apoptosis. This study examines its expression pattern, site of production, and levels in the amniotic fluid (AF) during pregnancy complications such as preterm labor and preterm premature rupture of membranes (pPROM). The ability of IL-18 to induce the Fas–Fas ligand (FasL)/caspase-mediated apoptotic pathway is also studied.
Methods: Amniochorion collected at term was placed in an organ explant system. IL-18 mRNA expression was studied by RT-PCR. IL-18 mRNA and peptide were localized by in situ hybridization and immunohistochemistry. IL-18 in the AF of women with pPROM, with preterm labor with no rupture of membranes, and at term was measured using ELISA. Multiplex PCR was used to study the expression pattern of proapoptotic genes such as Fas, FasL, caspase 8, and Fas-associated death domain (FADD). ELISA was also used to measure the release of soluble Fas from IL-18-stimulated amniochorion in culture media.
Results: IL-18 is a constitutively expressed gene in human chorion and decidua but not in human amnion and increases in the AF of women with pPROM [2.9 ± 3.3 ng/ml (SD)] compared to women with preterm labor (1.1 ± 0.67 ng/ml; P < 0.05) and term (0.9 ± 0.73 ng/ml; P < 0.05). IL-18 induces Fas expression, whereas FADD is a constitutively expressed gene in human fetal membranes. IL-18 failed to induce FasL or caspase 8 expressions. Soluble Fas release from amniochorion was increased after IL-18 stimulation.
Conclusion: Chorion and decidua are a source of IL-18, whose concentrations are increased in the AF during pPROM. IL-18 induced Fas expression in amniochorion; however, it failed to turn on other genes in the Fas–FasL apoptosis pathway including FasL and caspase 8.
Keywords: IL-18, apoptosis, Fas–FasL, PROM, amniotic fluid, fetal membranes
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