Problem: The inflammatory-anti-inflammatory cytokine network is thought to play a critical role in regulated progression and termination of pregnancy. The aim of this study was to evaluate the effects of interferon (IFN)-gamma on the expression of Cyclooxygenase (COX)-2 and production of prostaglandin E(2) (PGE(2)) in the human placenta from term and preterm labor deliveries.
Method of study: Placental explant culture system was used. COX-2 expression was determined by complementary techniques of immunohistochemistry and Western blotting. Released IFN-gamma and PGE(2) by placental explants were measured by enzyme-linked immunosorbent assay. Signal transducer and activator of transcription 1 (STAT1) phosphorylation was evaluated by Western blotting using a specific antibody.
Results: IFN-gamma was poorly detected in the placenta but was significantly expressed in decidual tissues from both term and preterm pregnancies as detected by immunohistochemistry. IFN-gamma significantly inhibited COX-2 expression and PGE(2) release in cultured placental explants from term and preterm labor deliveries. This effect most likely occurred in a STAT1-dependent manner as this regulatory protein was phosphorylated in response to IFN-gamma. IFN-gamma receptor (IFN-gammaR) was expressed in normal early pregnancy placental samples. However, its expression was significantly reduced in placental samples from term and preterm deliveries. Of interest, IFN-gammaR was expressed in placentas from term and preterm labor deliveries after 24 hr in culture.
Conclusions: Our data suggest that the human placenta is an important site for IFN-gamma-mediated repression of COX-2 expression and PGE2 production, implying that functional withdrawal of IFN-gamma may be involved in the onset of term or preterm labor.